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1.
Artículo en Chino | WPRIM (Pacífico Occidental) | ID: wpr-1036225

RESUMEN

ObjectiveTo investigate the effect and mechanism of Zhenwutang on renal oxidative damage in the mouse model of diabetic kidney disease with the syndrome of spleen-kidney Yang deficiency via the nuclear factor erythroid 2-related factor-2 (Nrf2)/heme oxygenase-1 (HO-1)/glutathione peroxidase 4 (GPX4) signaling pathway. MethodTwenty-five 7-week-old SPF-grade male db/m mice and 95 7-week-old SPF-grade male db/db mice were adaptively fed for a week. A blank group was set with the db/m mice without treatment, and the other mice were administrated with Rhei Radix et Rhizoma decoction and hydrocortisone for the modeling of diabetic kidney disease with the syndrome of spleen-kidney Yang deficiency. The modeled mice were randomized into the model, irbesartan (25 mg·kg-1), and high-, medium-, low-dose (33.8, 16.9, 8.45 g·kg-1) Zhenwutang groups (n=15) and administrated with corresponding drugs for 8 weeks. The survival status of mice was observed, and the traditional Chinese medicine (TCM) syndrome score was recorded. The indicators related to spleen-kidney Yang deficiency, fasting blood glucose (FBG), and renal function indicators were determined. Hematoxylin-eosin staining was employed to observe the histopathological changes of the renal tissue in each group. Biochemical kits were used to determine the oxidative stress-related indicators in the renal tissue. Real-time polymerase chain reaction and Western blotting were employed to determine the mRNA and protein levels, respectively, of Nrf2, HO-1, glutamate-cysteine ligase catalytic subunit (GCLC), and GPX4 in the renal tissue of mice in each group. ResultCompared with the blank group, the modeling increased the TCM syndrome score (P<0.05), elevated the estradiol (E2) and FBG levels (P<0.05), lowered the testosterone (T), triiodothyronine (T3), and tetraiodothyronine (T4) levels (P<0.05), and weakened the renal function (P<0.05). In addition, the modeling led to glomerular hypertrophy and glomerular mesangial and basal thickening, decreased the catalase (CAT) activity, total antioxidant capacity (T-AOC), and glutathione (GSH) content (P<0.05), increased the malondialdehyde (MDA) content (P<0.05), and down-regulated the mRNA and protein levels of Nrf2, HO-1, GCLC, and GPX4 in the renal tissue (P<0.05). Compared with the model group, high and medium doses of Zhenwutang decreased the TCM syndrome score and E2 content (P<0.05), increased the T, T3, and T4 content (P<0.05), improved the renal function (P<0.05), alleviated the pathological changes in the renal tissue, increased CAT, T-AOC, and GSH (P<0.05), reduced MDA (P<0.05), and up-regulated the mRNA and protein levels of Nrf2, HO-1, GCLC, and GPX4 in the renal tissue (P<0.05). ConclusionZhenwutang can improve the general state and renal function and reduce the oxidative damage and pathological changes in the renal tissue of db/db mice with spleen-kidney Yang deficiency by regulating the Nrf2/HO-1/GPX4 signaling pathway.

2.
Artículo en Chino | WPRIM (Pacífico Occidental) | ID: wpr-1012687

RESUMEN

ObjectiveThis study aims to examine the effect of Rhei Radix et Rhizoma-Coptidis Rhizoma on reducing insulin resistance in db/db mice by regulating the adenylate activated protein kinase (AMPK)/UNC-51-like kinase 1 (ULK1)/key molecule of autophagy, benzyl chloride 1 (Beclin1) pathway and elucidate the underlying mechanism. MethodSixty 6-week-old male db/db mice were studied. They were randomly divided into the model group, metformin group (0.26 g·kg-1), and low-, middle-, and high-dose groups (2.25, 4.5, 9 g·kg-1) of Rhei Radix et Rhizoma-Coptidis Rhizoma. A blank group of db/m mice of the same age was set, with 12 mice in each group. After eight weeks of continuous intragastric administration, the blank group and model group received distilled water intragastrically once a day. The survival status of the mice was observed, and fasting blood glucose (FBG) was measured using a Roche blood glucose device. Fasting serum insulin (FINS) was measured using an enzyme-linked immunosorbent assay, and the insulin resistance index (HOMA-IR) was calculated. Hematoxylin-eosin (HE) staining was performed to observe the pathological changes in the liver of the mice. The protein expression levels of AMPK, Beclin1, autophagy associated protein 5 (Atg5), and p62 in liver tissue were determined by using Western blot. The protein expression levels of autophagy associated protein 1 light chain 3B (LC3B) and ULK1 in liver tissue were determined using immunofluorescence. Real-time fluorescence quantitative PCR (Real-time PCR) was used to measure mRNA expression levels of AMPK, Beclin1, Atg5, ULK1, and p62. ResultCompared with the blank group, the model group exhibited a significant increase in body mass (P<0.01). Additionally, the levels of FBG, FINS, and HOMA-IR significantly changed (P<0.01). The structure of liver cells was disordered. The protein expression levels of AMPK, Beclin1, and Atg5 in liver tissue were significantly decreased (P<0.01), while the expression level of p62 protein was significantly increased (P<0.01). The expression levels of mRNA and proteins were consistent. Compared with the model group, the body mass of the metformin group and high and medium-dose groups of Rhei Radix et Rhizoma-Coptidis Rhizoma was significantly decreased (P<0.05). FBG, FINS, and HOMA-IR were significantly decreased (P<0.05,P<0.01). After treatment, the liver structure damage in each group was alleviated to varying degrees. The protein expressions of AMPK, Beclin1, Atg5, LC3B, and ULK1 were increased (P<0.05,P<0.01), while the protein expression of p62 was decreased (P<0.01). The expression levels of mRNA and proteins were generally consistent. ConclusionThe combination of Rhei Radix et Rhizoma-Coptidis Rhizoma can effectively improve liver insulin resistance, regulate the AMPK autophagy signaling pathway, alleviate insulin resistance in db/db mice, and effectively prevent the occurrence and development of type 2 diabetes.

3.
Artículo en Chino | WPRIM (Pacífico Occidental) | ID: wpr-1011451

RESUMEN

ObjectiveTo investigate the effect and mechanism of Shenqi Tangluo pill (SQTLP) on oxidative stress injury of skeletal muscle of type 2 diabetes mellitus (T2DM) mice based on nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1)/NAD(P)H quinone oxidoreductase 1 (NQO1) pathway. MethodA total of 60 7-week-old male db/db mice [specific pathogen-free (SPF) grade] were selected and fed for one week for adaption. They were divided into the model control group, SQTLP low-, medium- and high-dose (19, 38, and 76 g·kg-1) groups and metformin group (0.26 g·kg-1) by gavage. Each group consisted of 12 mice. Twelve male db/m mice of the same age were selected as the blank group. The intervention was implemented continuously for 8 weeks. Fasting blood glucose (FBG) was detected. Fasting serum insulin (FINS) levels were detected by enzyme-linked immunosorbent assay (ELISA), and the homeostasis model assessment-insulin resistance (HOMA-IR) index and the homeostasis model assessment-insulin sensitivity index (HOMA-ISI) were calculated. Oral glucose tolerance test (OGTT) and insulin tolerance test (ITT) were conducted. The activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) and the contents of malondialdehyde (MDA) and reduced nicotinamide adenine dinucleotide phosphate (NADPH) in skeletal muscle tissues were detected by biochemical kits. Hematoxylin-eosin (HE) staining was used to observe the pathological changes in skeletal muscle tissues. The levels of reactive oxygen species (ROS) and 4-hydroxynonenal (4-HNE) in skeletal muscle tissue were detected by immunofluorescence (IF). The expression levels of Nrf2, HO-1, NQO1 and glutamate-cysteine ligase catalytic subunit (GCLC) proteins in skeletal muscle tissues were detected by Western blot. ResultCompared with those in the blank group, FBG, FINS and HOMA-IR in the model group were significantly increased (P<0.05), while HOMA-ISI was decreased (P<0.05). The results of OGTT and ITT showed that blood glucose was significantly increased at all time points (P<0.05), and glucose tolerance and insulin tolerance were significantly impaired. SOD and GSH-Px activities in skeletal muscle tissues were significantly decreased (P<0.05), and MDA and NADPH contents were significantly increased (P<0.05). In skeletal muscle tissues, the arrangement of muscle fibers was loose, the nucleus was disordered, and inflammatory cells were infiltrated. The expression levels of ROS and 4-HNE in skeletal muscle tissues were significantly increased (P<0.05). The protein expression levels of Nrf2, HO-1, NQO1 and GCLC in skeletal muscle tissues were significantly decreased (P<0.05). Compared with those in the model group, FBG, FINS and HOMA-IR in the metformin group were significantly decreased (P<0.05), while HOMA-ISI was increased (P<0.05). The results of OGTT and ITT showed that blood glucose in the metformin group was significantly decreased at all time points (P<0.05). The activities of SOD and GSH-Px in skeletal muscle tissues were significantly increased (P<0.05), while the contents of MDA and NADPH were significantly decreased (P<0.05). No obvious abnormality was found in the skeletal muscle tissue of the metformin group. The expressions of ROS and 4-HNE in skeletal muscle tissues were decreased (P<0.05). The protein expression levels of Nrf2, HO-1, NQO1 and GCLC in skeletal muscle tissues were significantly increased (P<0.05). Compared with those in the model group, FBG, FINS and HOMA-IR in the SQTLP medium- and high-dose groups were significantly decreased (P<0.05), while HOMA-ISI was increased (P<0.05). The results of OGTT and ITT showed that the glucose tolerance and insulin tolerance of mice were improved in each dose group of SQTLP. The GSH-Px activity in the SQTLP low-dose group was significantly increased (P<0.05), and the NADPH content was decreased (P<0.05). The activities of SOD and GSH-Px in the SQTLP medium- and high-dose groups were significantly increased (P<0.05), while the contents of MDA and NADPH were significantly decreased (P<0.05). The skeletal muscle tissue injury of mice in each dose group of SQTLP was ameliorated to different degrees. In the SQTLP medium- and high-dose groups, the expressions of ROS and 4-HNE were decreased (P<0.05), and the protein expression levels of Nrf2, HO-1, NQO1 and GCLC were significantly increased (P<0.05). Compared with those in the SQTLP low-dose group, FBG and HOMA-IR in the SQTLP high-dose group were significantly decreased (P<0.05), while HOMA-ISI was increased (P<0.05). The results of OGTT and ITT showed that the SQTLP high-dose group significantly improved the glucose tolerance and insulin tolerance of mice. The activities of SOD and GSH-Px in skeletal muscle tissues were significantly increased (P<0.05), while the contents of MDA and NADPH were significantly decreased (P<0.05). No obvious abnormality was found in the skeletal muscle tissue, the expressions of ROS and 4-HNE were decreased (P<0.05), and the protein expression levels of Nrf2, HO-1, NQO1 and GCLC were significantly increased (P<0.05) in the skeletal muscle tissue of the SQTLP high-dose group. ConclusionSQTLP can significantly improve IR in T2DM mice, and the mechanism is related to SQTLP activating the Nrf2/HO-1/NQO1 signaling pathway, promoting the expression of antioxidant enzymes, and thus improving the oxidative stress injury in the skeletal muscle.

4.
Chinese Journal of Immunology ; (12): 586-591, 2024.
Artículo en Chino | WPRIM (Pacífico Occidental) | ID: wpr-1024767

RESUMEN

Objective:To investigate the tumor suppressing effect of Shenqi Yiliu decoction combined with cisplatin via ERK-mediated C-Myc/PD-L1 phase-coordinated pathway on H22 hepatocellular carcinoma tumor-bearing mice and its mechanism.Meth-ods:In 60 SPF-grade male Kunming mice,10 mice were taken as blank group by random number table method,and the other 50 mice were replicated as H22 hepatocellular carcinoma tumor-bearing mouse model.After successful replication of the model,the model mice were randomly divided into model group,cisplatin group[2.5×10-3 g/(kg·3 d)],Shenqi Yiliu decoction low[13.515 g/(kg·d)],me-dium[27.03 g/(kg·d-1)],and high dose[27.030 g/(kg·d)]combined with cisplatin group[2.5×10-3 g/(kg·3 d)],10 mice in each group were treated for 13 d.After 24 h of the last dose,the mice were anesthetized and sacrificed,and the tumor inhibition rate,spleen index and thymus index of each drug group were determined;HE staining was performed to observe the histopathological changes of tumor in mice;ELISA kit was used to detect the contents of EGF and IFN-γ in tumor tissue homogenate;p-ERK1/2,C-Myc and PD-L1 protein expression in tumor tissue were detected by IHC and Western blot;ERK,C-Myc and PD-L1 mRNA expression levels in tumor tissue were detected by RT-PCR.Results:Compared with blank group,the average body mass and spleen index of mice in model group were decreased(P<0.05).Compared with model group,the tumor inhibition effect of each treatment group was obvious,and Shenqi Yiliu decoction combined with cisplatin group inhibited tumor growth in liver cancer mice in a dose-dependent way,im-proved the average body mass,spleen index and thymus index of mice,promoted the necrosis of tumor cells and increased the necrotic area.EGF and IFN-γ contents,P-ERK1/2,C-Myc,PD-L1 protein expressions and ERK,C-Myc,PD-L1 mRNA expression levels were decreased in tumor tissues(P<0.05).Compared with cisplatin group,the therapeutic effect of Shenqi decoction combined with cisplatin in medium and high dose groups was significant,and the difference was statistically significant(P<0.05).Conclusion:Shenqi Yiliu decoction combined with cisplatin effectively inhibited the tumor growth of H22 liver cancer tumor-bearing mice and significantly reduces the expression of C-Myc and PD-L1 proteins in the tumor tissues,which may be through the regulation of ERK signaling path-way-related protein expression to exert tumor suppressive effect.

5.
Artículo en Chino | WPRIM (Pacífico Occidental) | ID: wpr-953917

RESUMEN

ObjectiveTo explore the intervention mechanism of Xiangsha Liujunzi Tang in rats with functional dyspepsia (FD) based on the Ras homolog gene family member A (RhoA)/Rho-associated coiled-coil containing protein kinase 2 (ROCK2)/Myosin phosphatase target Subunit 1 (MYPT1) pathway. MethodSixty male SD suckling rats in SPF grades were randomly divided into blank group (n=10) and model group (n=50). The comprehensive modeling method (gavage administration of iodoacetamide+exhaustion of swimming+disturbance of hunger and satiety) was used to replicate the rat model of FD. After successful replication of the model, the rats in the model group were randomly divided into model group, mosapride group, and high, middle, and low-dose Xiangsha Liujunzi Tang groups, with 10 rats in each group. Rats in the blank group and model group were given 10 mL kg-1·d-1 normal saline, those in the mosapride group were given 1.35 mg·kg-1·d-1 mosapride, and those in the high, middle, and low-dose Xiangsha Liujunzi Tang groups were given 12, 6, and 3 g·kg-1·d-1 Xiangsha Liujunzi Tang, respectively. The intervention lasted 14 days. The general living conditions of rats were observed before and after modeling and administration, and the 3-hour food intake and body mass of rats were measured. After intervention, the intestinal propulsion rate of rats was measured, and the pathological changes in the gastric tissue were observed by hematoxylin-eosin (HE) staining. The content of choline acetyl transferase (ChAT) and vasoactive intestinal peptide (VIP) in the medulla oblongata and gastric tissue homogenate was determined by enzyme-linked immunosorbent assay (ELISA), the distribution of adenosine triphosphate (ATP) enzyme in gastric antrum smooth muscle was observed by frozen section staining, and the protein expression levels of RhoA, ROCK2, and phosphorylated-myosin phosphatase target subunit 1 (p-MYPT1) in the gastric tissue were detected by Western blot. ResultCompared with the blank group, the model group had withered hair, lazy movement, slow action, poor general living condition, lower 3-hour food intake, body mass, and lower intestinal propulsion rate (P<0.05), whereas no obvious abnormality in gastric histopathology. In the model group, the content of ChAT in the medulla oblongata and gastric tissue decreased, the content of VIP in gastric tissue increased, the distribution of ATP enzyme in gastric antrum smooth muscle decreased significantly, and the protein expression levels of RhoA, ROCK2, and p-MYPT1 in the gastric tissue decreased significantly (P<0.05). As compared with the model group, the general living condition of rats in each intervention group was significantly improved, and the 3-hour food intake, body mass, and intestinal propulsion rate were significantly increased (P<0.05). There was no significant difference in gastric pathology in the intervention groups. The content of ChAT in the medulla oblongata and gastric tissue increased significantly, the content of VIP in the gastric tissue decreased, the distribution of ATP enzyme in gastric antrum smooth muscle increased significantly, and the protein expression levels of RhoA, ROCK2, and p-MYPT1 in the gastric tissue increased significantly (P<0.05). The intervention effect of Xiangsha Liujunzi Tang group on the above indexes was dose-dependent. ConclusionXiangsha Liujunzi Tang can effectively improve the general living condition and gastric motility of rats with FD, and its specific mechanism may be related to the activation of the RhoA/ROCK2/MYPT1 pathway in the gastric tissue to regulate smooth muscle relaxation and contraction and promote gastric motility.

6.
Artículo en Chino | WPRIM (Pacífico Occidental) | ID: wpr-984577

RESUMEN

ObjectiveTo explore the mechanism of Dahuang Mudantang in alleviating the intestinal injury in the rat model of acute pancreatitis via the high-mobility group box 1 (HMGB1)/receptor for advanced glycation endproduct (RAGE)/nuclear factor-κB (NF-κB) signaling pathway. MethodOne hundred and twenty SPF-grade Wistar rats received retrograde injection of 5% sodium taurocholate into the biliopancreatic duct for the modeling of intestinal injury in acute pancreatitis. The rats were randomized into blank, model, low-, medium-, and high-dose (3.5, 7, 14 g·kg-1, administrated by gavage) Dahuang Mudantang, and octreotide (1×10-5 g·kg-1, subcutaneous injection) groups (n=20). The rats in blank and model groups received equal volume of distilled water by gavage. Drugs were administered 1 h before and every 12 h after modeling, and samples were collected 24 h after modeling. The general status of the rats was observed. The biochemical methods were employed to measure the levels of amylase (AMS) and C-reactive protein (CRP) in the serum. The enzyme-linked immunosorbent assay (ELISA) was employed to measure the levels of tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6 in the colon tissue. The morphological changes of pancreatic and colon tissues were observed by hematoxylin-eosin (HE) staining. Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR) and Western blot were employed to measure the expression levels of HMGB1, RAGE, inhibitor of NF-κB kinase (IKK), and NF-κB suppressor protein α(IκBα)in the colon tissue. ResultThe rats in the model group showed poor general survival, writhing response, reduced frequency of defecation, and dry stool. The symptoms of rats in the model group were mitigated in each treatment group, and the high-dose Dahuang Mudantang showed the most significant effect. Compared with the normal group, the model group had elevated AMS and CRP levels (P<0.05), which were lowered by Dahuang Mudantang (P<0.05), especially that at the high dose (P<0.05). Compared with the normal group, the modeling elevated that levels of TNF-α, IL-1β, and IL-6 (P<0.05). Such elevations were lowered by Dahuang Mudantang (P<0.05), and the high-dose group and the octreotide group showed better performance (P<0.05). The modeling caused necrotic, congested, and destructed pancreatic and colonic tissues, which were ameliorated by the drugs, especially high-dose Dahuang Mudantang. Compared with the normal group, the modeling up-regulated the mRNA levels of HMGB1, RAGE, IKK, IκBα, and NF-κB (P<0.05). Compared with the model group, Dahuang Mudantang and octreotide down-regulated the mRNA levels of HMGB1, RAGE, IKK, IκBα, and NF-κB (P<0.05), and the high-dose Dahuang Mudantang demonstrated the best performance (P<0.05). Western blot results showed a trend consistent with the results of Real-time PCR. ConclusionDahuang Mudantang can improved the general status, reduce inflammation, and alleviate histopathological changes in the pancreatic and colon tissues in the rat model of acute pancreatitis by inhibiting the HMGB1/RAGE/NF-κB signaling pathway.

7.
Artículo en Chino | WPRIM (Pacífico Occidental) | ID: wpr-988181

RESUMEN

ObjectiveTo reveal the intervention effect of Dahuang Mudantang on pancreatic injury in rats with acute pancreatitis (AP) of dampness-heat in large intestine syndrome and explore its possible mechanism based on network pharmacology. MethodNinety-six SPF-grade Wistar rats were randomly divided into the following six groups: a blank group, a model group, low-, medium-, and high-dose Dahuang Mudantang groups (3.5, 7, and 14 g·kg-1), and a Qingyi Lidan granules group (3 g·kg-1), with 16 rats in each group. The AP model of dampness-heat in large intestine syndrome was induced in rats except for those in the blank group by "high-temperature and high-humidity environment + high-sugar and high-fat diet + retrograde injection of 5% sodium taurocholate into the pancreaticobiliary duct". The blank and model groups received equal volumes of distilled water by gavage, while the treatment groups were administered Dahuang Mudantang or Qingyi Lidan granules 1 hour before modeling, and 12 and 24 hours after modeling. Samples were collected 1 hour after the last administration. The general conditions of the rats were observed. The AP model of dampness-heat in large intestine syndrome was evaluated. Serum amylase (AMS) and C-reactive protein (CRP) levels were determined using biochemical methods. Pancreatic tissue morphology was observed using hematoxylin-eosin (HE) staining. Network pharmacology was employed to predict potential targets of Dahuang Mudantang in the intervention in AP, and molecular biology technique was used to verify relevant targets. ResultCompared with the blank group, the model group exhibited lethargy, unkempt fur, loose and foul-smelling stools, elevated anal temperature with arching and twisting reactions, significantly increased serum levels of AMS and CRP (P<0.05), abnormal pancreatic ductules, disordered interlobular spaces, and inflammatory cell infiltration in histopathological examination, as well as pathological changes including pancreatic acinar cell swelling, congestion, and necrosis. Compared with the model group, the treatment groups showed varying degrees of improvement in general survival conditions, reduced twisting reactions, visibly improved stool characteristics, reduced pancreatic tissue edema and necrosis, decreased serum AMS and CRP levels (P<0.05), with the high-dose Dahuang Mudantang group showing the most pronounced effects (P<0.05). Network pharmacology prediction indicated that hederagenin, β-sitosterol, and quercetin were the most widely connected active compounds with disease targets. Protein-protein interaction (PPI) network analysis revealed that protein kinase B (Akt), tumor protein P53 (TP53), tumor necrosis factor (TNF), interleukin-6 (IL-6), transcription factor (JUN), vascular endothelial growth factor α (VEGFα), interleukin-1β (IL-1β), and vascular cell adhesion molecule-1 (VCAM1) were key targets in the "drug-disease" interaction. KEGG enrichment analysis suggested that the response of the mitogen activated protein kinase (MAPK) signaling pathway might be a core mechanism for DHMDT in the intervention in AP. Molecular biology analysis showed that compared with the blank group, the model group had significantly increased levels of TNF-α, IL-6, and VCAM-1 in pancreatic tissue (P<0.05), as well as significantly elevated expression levels of p38 mitogen-activated protein kinase (p38 MAPK), mitogen-activated protein kinase-activated protein kinase 2 (MK2), and human antigen R (HUR) genes and proteins (P<0.05). Compared with the model group, the treatment groups exhibited decreased levels of TNF-α, IL-6, and VCAM-1 in pancreatic tissue (P<0.05), reduced expression levels of p38 MAPK, MK2, and HUR genes and proteins, with the high-dose Dahuang Mudantang group showing the most pronounced effects (P<0.05). ConclusionDahuang Mudantang activates and regulates the p38 MAPK/MK2/HUR signaling pathway to suppress the release of inflammatory factors, thereby improving pancreatic injury.

8.
Artículo en Chino | WPRIM (Pacífico Occidental) | ID: wpr-1019698

RESUMEN

Objective Based on HMGB1/TLR4/NF-κB pathway,to investigate the effects of Shenqi Yiliu decoction combined with cisplatin on H22 liver cancer tumor mice and the effects of related immune indicators.Methods 50 SPF grade male KM mice,10 mice were taken as blank group by random number table method,and the other 40 mice were replicated as H22 hepatocellular carcinoma tumor-bearing mice model.After successful replication of the model,the model mice were randomly divided into model group,cisplatin group(2.5×10-3 g·kg-1),Shenqi Yiliu decoction TCM group(27.03 g·kg-1),and Shenqi Yiliu decoction TCM(27.03 g·kg-1)combined with cisplatin(2.5×10-3 g·kg-1),10 mice in each group were treated for 13 d.Determine tumor suppression rate,spleen index and thymus index;HE observes changes in oncology pathology;streaming cells detect the level of CD4+T,CD8+T cells in the spleen tissue;PT-PCR and WB method detect genes and protein expression related to HMGB1/TLR4/NF-κB signaling pathways in tumor tissues.Results ①Compared with the blank group,the mean body mass and mouse spleen index,thymus index,CD4+ T cell level and CD4+T/CD8+T value were significantly lower and CD8+T cell level was higher in the model group(P<0.05);②Compared with the model group,the mean tumor mass decreased(P<0.05),tumor volume decreased(P<0.05),and body mass increased(P<0.05)in each treatment group,and the spleen index,thymus index,CD4+T cell level and CD4+T/CD8+T ratio increased and CD8+T cell level decreased in both the Chinese medicine group and the combination group,and the treatment effect was significant in the Chinese medicine group(P<0.05),and HMGB1,TLR4,MyD88,NF-κB mRNA and protein expression in tumor tissues of mice were reduced,and the effect was significant in the combined group(P<0.05).③Compared with the cisplatin group,HMGB1,TLR4,MyD88,NF-κB mRNA and protein expression were reduced in the tumor tissues of mice in the combination group(P<0.05).④HMGB1,TLR4,MyD88,NF-κB mRNA and protein expression in tumor tissues of mice in the combined group were reduced compared with those in the Chinese medicine group(P<0.05).Conclusion Shenqi Yiliu decoction combined with cisplatin can effectively inhibit tumor growth and improve related immune indexes in H22 hepatocellular carcinoma tumor-bearing mice,and the mechanism may be related to the inhibition of HMGB1/TLR4/NF-κB signaling pathway activation.

9.
Artículo en Chino | WPRIM (Pacífico Occidental) | ID: wpr-997673

RESUMEN

Diabetic nephropathy (DN), a major cause of chronic kidney disease (CKD), aggravates the prevalence of end-stage renal disease (ESRD) and threatens human health. The pathogenesis of DN is complex, in which inflammation is a key pathological link in the cascade injury. Therefore, the treatment targeting inflammation helps to delay the progression of DN. NOD-like receptor protein 3 (NLRP3), a classical proteasome, acts as an inducer of innate immune responses. The activated NLRP3 inflammasomes produce and release inflammatory mediators to trigger pyroptosis and uncontrolled autophagy and mediate the stress signals promoting renal fibrosis, thus participating in the development and progression of DN. The NLRP3 inflammasome as a core site inducing inflammation is widely involved in DN progression and may be a novel target. The active components and compound prescriptions of Chinese medicines are increasingly applied in the prevention and treatment of DN. The latest studies have discovered that Chinese medicines can treat DN by regulating the activation of NLRP3 inflammasomes. Although studies have been conducted to explore the mechanism of Chinese medicines in the treatment of DN via NLRP3 inflammasome, the systematic review remains to be carried out. This paper reviews the relevant publications in recent years and introduces the research progress from the assembly and activation of NLRP3 inflammasomes, the mechanism of NLRP3 inflammasomes in the treatment of DN, and the regulation of NLRP3 inflammasomes by Chinese medicines for the prevention and treatment of DN, aiming to lay a foundation for the relevant studies and provide new targets and strategies for the prevention and treatment of DN.

10.
Artículo en Chino | WPRIM (Pacífico Occidental) | ID: wpr-996511

RESUMEN

ObjectiveTo explore the anti-tumor effect and mechanism of Shenqi Yiliu prescription in the intervention of pyroptosis. MethodTen male BALB/c mice were randomly selected and assigned to the blank group. The remaining 40 mice underwent the induction of the liver cancer xenograft model. After 5 days of modeling, 40 surviving mice were randomly divided into model group, cisplatin group [2.5×10-3 g·kg-1·(3 d)-1], Shenqi Yiliu prescription group (27 g·kg-1·d-1), and a combination group (Shenqi Yiliu prescription group + cisplatin). The mice in the blank group and the model group were treated with an equal volume of normal saline for 10 days. The general conditions of mice in each group were observed. After the intervention, the tumor weight of the mice was weighed and the tumor inhibition rate was calculated. Hematoxylin-eosin (HE) staining was used to observe the pathological changes in tumor tissues. The levels of mouse liver function indicators, including alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were detected. The TdT-mediated dUTP-biotin nick end labeling (TUNEL) assay was used to detect DNA damage in mouse tumor tissue cells. Immunohistochemistry (IHC), immunofluorescence (IF), and Western blot were used to detect the protein expression levels of NOD-like receptor protein 3 (NLRP3), cysteinyl aspartate-specific protease-1 (Caspase-1), and gasdermin D (GSDMD) in tumor tissues. The levels of interleukin-1β (IL-1β) and interleukin-18 (IL-18) in tumor tissues were detected by enzyme-linked immunosorbent assay (ELISA). ResultCompared with the mice in the blank group, those in the model group were in a poor mental state, sleepy, and lazy, and their fur color was dull, with increased levels of serum ALT and AST in liver function tests (P<0.01). Compared with the model group, the groups with drug intervention showed improved mental state, inhibited tumor growth to varying degrees, and decreased tumor weight, and the tumor inhibition rate in the combination group was the highest (P<0.01). HE staining showed that the pathological and morphological lesions of the tumor tissues in the model group were significant, while those in all groups with drug intervention were improved to a certain extent. The karyolysis and nuclear rupture in the Shenqi Yiliu prescription group and the combination group were more significant. In the liver function test, the serum ALT and AST levels of mice in the Shenqi Yiliu prescription group and the combination group decreased (P<0.01), and the inflammatory factors IL-1β and IL-18 in each group with drug intervention decreased (P<0.05, P<0.01). Among them, the declining trend of IL-1β and IL-18 in the Shenqi Yiliu prescription group was the most significant (P<0.01). TUNEL staining showed that the positive TUNEL staining in each group with drug intervention decreased after intervention (P<0.05, P<0.01), especially the cisplatin group and Shenqi Yiliu prescription group (P<0.01). Western blot, IHC, and IF found that the protein expression levels of NLRP3, Caspase-1, and GSDMD in each group with drug intervention decreased (P<0.05, P<0.01). Compared with the mice in the cisplatin group, those in the Shenqi Yiliu prescription group and the combination group had better mental state and regular tumor morphology, and the tumor weight of the mice in the combination group decreased (P<0.05). The levels of ALT and AST in the Shenqi Yiliu prescription group decreased (P<0.05), and the levels of IL-1β and IL-18 in the Shenqi Yiliu prescription group and the combination group decreased (P<0.05, P<0.01), especially in the combination group (P<0.01). The results of IHC showed that the expression of GSDMD protein in the tumor tissues of mice in the combination group was reduced (P<0.01). IF detection showed that the expression of NLRP3 in the tumor tissues of the Shenqi Yiliu prescription group was reduced (P<0.01). The results of Western blot showed that the expression level of NLRP3 protein in the Shenqi Yiliu prescription group and the combination group decreased (P<0.01), and the expression level of Caspase-1 protein in the combination group decreased (P<0.01). The decrease in GSDMD protein expression was not significant, and the difference was not statistically significant. ConclusionShenqi Yiliu prescription combined with cisplatin has an obvious anti-tumor effect, which may be achieved by down-regulating the NLRP3/Caspase-1/GSDMD inflammatory pyroptosis pathway to inhibit cell pyroptosis, and relieve the inflammatory response in mice with liver cancer.

11.
Artículo en Chino | WPRIM (Pacífico Occidental) | ID: wpr-1008674

RESUMEN

To investigate the intervention effect and mechanism of Zhenwu Decoction on diabetic nephropathy(DN) mice of spleen-kidney Yang deficiency syndrome based on the Rho-associated coiled-coil kinase(ROCK)/IκB kinase(IKK)/nuclear factor-κB(NF-κB) pathway. Ninety-five 7-week-old db/db male mice and 25 7-week-old db/m male mice were fed adaptively for one week. The DN model of spleen-kidney Yang deficiency syndrome was induced by Dahuang Decoction combined with hydrocortisone by gavage, and then the model was evaluated. After modeling, they were randomly divided into a model group, high-dose, medium-dose, and low-dose Zhenwu Decoction groups(33.8, 16.9, and 8.45 g·kg~(-1)·d~(-1)), and an irbesartan group(25 mg·kg~(-1)·d~(-1)), with at least 15 animals in each group. The intervention lasted for eight weeks. After the intervention, body weight and food intake were measured. Serum crea-tinine(Scr), blood urea nitrogen(BUN), fasting blood glucose(FBG), urinary albumin(uALb), and urine creatinine(Ucr) were determined. The uALb/Ucr ratio(ACR) and 24 h urinary protein(UTP) were calculated. Renal pathological morphology was evaluated by HE staining and Masson staining. The levels of key molecular proteins in the ROCK/IKK/NF-κB pathway were detected by Western blot. Enzyme-linked immunosorbent assay(ELISA) was used to detect interleukin-1β(IL-1β), interleukin-6(IL-6), interleukin-8(IL-8), interleukin-10(IL-10), and tumor necrosis factor-α(TNF-α). Compared with the blank group, the model group showed increased content of BUN, uALb, and SCr, increased values of 24 h UTP and ACR, decreased content of Ucr(P<0.05), enlarged glomeruli, thickened basement membrane, mesangial matrix proliferation, inflammatory cell infiltration, and collagen fiber deposition. The protein expression of ROCK1, ROCK2, IKK, NF-κB, phosphorylated IKK(p-IKK), phosphorylated NF-κB(p-NF-κB), and phosphorylated inhibitor of NF-κB(p-IκB) increased(P<0.05), while the protein expression of inhibitor of NF-κB(IκB) decreased(P<0.05). The levels of inflammatory factors IL-1β, IL-6, IL-8, and TNF-α increased(P<0.05), while the level of IL-10 decreased(P<0.05). Compared with the model group, the groups with drug treatment showed decreased levels of BUN, uALb, SCr, 24 h UTP, and ACR, increased level of Ucr(P<0.05), and improved renal pathological status to varying degrees. The high-and medium-dose Zhenwu Decoction groups and the irbesartan group showed reduced protein expression of ROCK1, ROCK2, IKK, NF-κB, p-IKK, p-NF-κB, and p-IκB in the kidneys(P<0.05), increased protein expression of IκB(P<0.05), decreased levels of serum inflammatory factors IL-1β, IL-6, IL-8, and TNF-α(P<0.05), and increased level of IL-10(P<0.05). Zhenwu Decoction can significantly improve renal function and renal pathological damage in DN mice of spleen-kidney Yang deficiency syndrome, and its specific mechanism may be related to the inhibition of inflammatory response by down-regulating the expression of key molecules in the ROCK/IKK/NF-κB pathway in the kidney.


Asunto(s)
Ratones , Masculino , Animales , FN-kappa B/metabolismo , Interleucina-8 , Interleucina-10 , Factor de Necrosis Tumoral alfa/metabolismo , Interleucina-6 , Quinasa I-kappa B , Bazo , Irbesartán , Uridina Trifosfato , Deficiencia Yang/tratamiento farmacológico , Riñón/patología
12.
Asian Journal of Andrology ; (6): 201-206, 2022.
Artículo en Inglés | WPRIM (Pacífico Occidental) | ID: wpr-928532

RESUMEN

Contrast-enhanced ultrasound (CEUS) is a new form of ultrasound (US) that can dynamically display microvessels in a highly sensitive manner. The purpose of this study was to investigate the efficacy of CEUS for characterizing testicular lesions in comparison with conventional US. Forty-seven patients with testicular lesions were enrolled. The histopathology results revealed that 31 cases were neoplastic (11 cases of seminomas, 8 nonseminomatous germ cell tumors, 8 lymphomas, 2 Leydig cell tumors, and 2 nonspecific tumors), and 16 cases were nonneoplastic (8 cases of infarctions, 3 epidermoid cysts, and 5 inflammation). The indicators of shallow lobulated morphology and cystic-solid echogenicity on conventional US were suggestive of germ cell tumors. More indicators on CEUS were found to be useful for characterizing testicular lesions. All the neoplastic lesions showed hyperenhancement on CEUS. Moreover, germ cell tumors presented with heterogeneous enhancement (73.7%, 14/19), a twisted blood vessel pattern, rapid wash-in and wash-out, and peripheral rim hyperenhancement signs. Lymphoma was characterized by nonbranching linear vessel patterns (87.5%, 7/8), rapid wash-in and slow wash-out. In nonneoplastic lesions, infarction and epidermoid cysts showed no enhancement, and abscesses were observed with marginal irregular enhancement. The sensitivity, specificity, and accuracy of CEUS for differentiating between neoplastic and nonneoplastic lesions were 100%, 93.8%, and 97.9%, respectively, and these values were higher than those for conventional US (90.3%, 62.5%, and 80.9%, respectively). CEUS can sensitively reflect the microvascular perfusion in testicular lesions and offers high accuracy for characterizing them.


Asunto(s)
Humanos , Masculino , Medios de Contraste , Diagnóstico Diferencial , Quiste Epidérmico , Linfoma , Neoplasias de Células Germinales y Embrionarias/diagnóstico por imagen , Sensibilidad y Especificidad , Neoplasias Testiculares/diagnóstico por imagen , Ultrasonografía/métodos
13.
Artículo en Chino | WPRIM (Pacífico Occidental) | ID: wpr-927376

RESUMEN

OBJECTIVE@#To observe the effect of moxibustion at "Guanyuan" (CV 4) and "Shenque" (CV 8) on acetylcholine (Ach), adenosine triphosphate (ATP) and muscarinic-type choline receptor (M2) and purine receptor P2X3 in bladder tissue in the rats with neurogenic bladder (NB) of detrusor areflexia after lumbar-sacral spinal cord injury and explore the underlying mechanism of moxibustion for promoting detrusor contraction.@*METHODS@#Sixty SD rats were randomly divided into a model preparation group (n=45) and a sham-operation group (n=15). In the model preparation group, the modified Hassan Shaker spinal cord transection method was used to prepare the model of NB. In the sham-operation group, the spinal cord transection was not exerted except laminectomy and spinal cord exposure. Among the rats with successfully modeled, 30 rats were selected and divided randomly into a model group and a moxibustion group, with 15 rats in each one. On the 15th day after the operation, moxibustion was applied at "Guanyuan" (CV 4) and "Shenque" (CV 8) in the moxibustion group, 10 min at each acupoint, once a day. The consecutive 7-day treatment was as one course and the intervention for 2 courses was required. Urodynamic test was adopted to evaluate bladder function in rats. Using HE staining, the morphological changes in bladder tissue were observed. The content of Ach and ATP in bladder tissue was measured with biochemical method, and the protein and mRNA expression levels of M2 and P2X3 receptors in bladder tissue were detected with Western blot and real-time fluorescence quantification PCR method.@*RESULTS@#Compared with the sham-operation group, the maximum bladder capacity, leakage point pressure and bladder compliance were increased in the rats of the model group (P<0.05). Compared with the model group, the maximum bladder capacity, the leakage point pressure and bladder compliance were decreased in the rats of the moxibustion group (P<0.05). In the model group, the detrusor fibres were arranged irregularly, bladder epithelial tissues were not tightly connected and cell arrangement was disordered, combined with a large number of vacuolar cells. In the moxibustion group, compared with the model group, the detrusor fibres were arranged regularly, bladder epithelial cells were well distributed and vacuolar cells were reduced. Compared with the sham-operation group, the content of Ach and ATP in bladder tissue was decreased (P<0.05), the protein and mRNA expression levels of M2 and P2X3 receptors were reduced (P<0.05) in the model group. In the moxibustion group, the content of Ach and ATP in bladder tissue was increased (P<0.05) and the protein and mRNA expression levels of M2 and P2X3 receptors were increased (P<0.05) as compared with the model group.@*CONCLUSION@#Moxibustion at "Guanyuan" (CV 4) and "Shenque" (CV 8) may effectively improve bladder function in the rats with NB of detrusor areflexia after lumbar-sacral spinal cord injury and its underlying mechanism is related to promoting the release of Ach and up-regulating the expression of M2 receptor, thereby enhancing the release of ATP and increasing the expression of P2X3 receptor. Eventually, detrusor contraction is improved.


Asunto(s)
Animales , Ratas , Moxibustión/métodos , Ratas Sprague-Dawley , Receptores Purinérgicos P2X3/metabolismo , Traumatismos de la Médula Espinal/terapia , Vejiga Urinaria , Vejiga Urinaria Neurogénica/terapia
14.
Cancer Research and Clinic ; (6): 521-524, 2022.
Artículo en Chino | WPRIM (Pacífico Occidental) | ID: wpr-958886

RESUMEN

Objective:To investigate the effects of solute carrier family 39 (SLC39) A14 on proliferation, migration and invasion of diffuse large B-cell lymphoma (DLBCL) OCI-LY3 cells.Methods:The human DLBCL cell line OCI-LY3 was divided into Vector group (transfected with empty control plasmid) and SLC39A14 group (transfected with SLC39A14 plasmid). The proliferation of OCI-LY3 cells in the two groups was detected by CCK-8 method, the migration and invasion of cells were detected by Transwell method, and the expression level of SLC39A14 protein and the expressions of PI3K-AKT-mTOR signaling pathway-related proteins in OCI-LY3 cells were detected by Western blotting.Results:Compared with the Vector group, the cell proliferation ability in the SLC39A14 group was increased from day 3 to day 5 (all P < 0.05).The results of Transwell cell migration assay showed that the number of migrating cells after 36 h in the Vector group was (64±4) cells, and that in the SLC39A14 group was (236±25) cells. The cell migration ability in the SLC39A14 group was increased, and the difference was statistically significant ( t = 15.02, P < 0.05). The results of Transwell cell invasion assay showed that the number of invasive cells in the Vector group was (32±2) cells, and that in the SLC39A14 group was (127±17) cells. The cell invasion ability in the SLC39A14 group was increased, and the difference was statistically significant ( t = 8.33, P < 0.05).The results of Western blotting showed that the expression levels of pmTOR, pAKT and pPI3K proteins in the SLC39A14 group were all increased. Conclusions:SLC39A14 may be involved in the occurrence and development of DLBCL through PI3K-AKT-mTOR signaling pathway.

15.
Cancer Research and Clinic ; (6): 681-684, 2021.
Artículo en Chino | WPRIM (Pacífico Occidental) | ID: wpr-912947

RESUMEN

Objective:To investigate the variation trend of peripheral blood CD34 + cells during the hematopoietic stem cell mobilization and its influence on the collection timing and results. Methods:The clinical data of 62 patients with hematologic diseases undergoing autologous peripheral blood hematopoietic stem cell mobilization from April 2012 to March 2017 in Shanxi Provincial Cancer Hospital were analyzed. Mobilization regimen used chemotherapy combined with granulocyte colony-stimulating factor (G-CSF) to monitor the number of white blood cells (WBC), mononuclear cells (MNC), CD34 + cells in peripheral blood and apheresis concentrates, and the correlation with CD34 + cells was analyzed. Furthermore, the receiver operating characteristic (ROC) curve was used to establish the threshold to start apheresis. Results:MNC (5.66±1.11)×10 8/kg and CD34 + cell count (2.15±1.20)×10 6/kg were obtained in 62 patients who received 136 times collection in total. The peak of peripheral blood CD34 + cells count appeared at day 4-5 after the treatment of G-CSF, and then it went down. CD34 + cell count in the product was correlated with the peripheral blood CD34 + cell count collected on the day ( r = 0.879, P < 0.01), and it was also correlated with the peripheral blood WBC and MNC collected on the day as well as MNC count in the product (all P < 0.05). Furthermore, the ROC curve analysis demonstrated that peripheral blood CD34 + cells count > 23/μl was the optimal threshold for stem cell collection on the day, 85.2% of patients reaching up to the threshold could be successfully collected at one time. Conclusions:The variation trend of peripheral blood CD34 + cell count can guide the best time of stem cell collection in clinic. Peripheral blood CD34 + cell count is the reliable index to predict CD34 + cells count in the products. Peripheral blood CD34 + cells count > 23/μl could be used as the collection threshold.

16.
Artículo en Chino | WPRIM (Pacífico Occidental) | ID: wpr-942998

RESUMEN

Objective: To observe the incidence and treatment of radiation rectal injury complicated with anxiety, depression and somatic symptom disorder. Methods: A cross-sectional survey research method was carried out. Patients with radiation rectal injury managed by members of the editorial board of Chinese Journal of Gastrointestinal Surgery were the subjects of investigation. The inclusion criteria of the survey subjects: (1) patients suffered from pelvic tumors and received pelvic radiotherapy; (2) colonoscopy showed inflammatory reaction or ulcer in the rectum. Exclusion criteria: (1) patient had a history of psycho-somatic disease before radiotherapy; (2) patient was unable to use a smart phone, unable to read and understand the questions in the questionnaire displayed on the phone; (3) patient refused to sign an informed consent form. According to the SOMA self-rating scale, PHQ-15 self-rating scale, GAD-7 and PHQ-9 self-rating scale, the electronic questionnaire of "Psychological Survey of Radiation Proctitis" was designed. The questionnaire was sent to patients with radiation rectal injury managed by the committee through the WeChat group. Observational indicators: (1) radiation rectal injury symptom assessment: using SOMA self-rating scale, radiation rectal injury symptom classification: mild group (≤3 points), moderate group (4-6 points) and severe group (> 6 points); (2) incidence of anxiety, depression and physical disorder: using GAD-7, PHQ-9 and PHQ-15 self-rating scales respectively for assessment; (3) correlation of radiation rectal injury symptom grading with anxiety, depression, and somatic symptom disorder. Results: Seventy-one qualified questionnaires were collected, of which 41 (56.9%) were from Guangzhou. Among the 71 patients, 6 were males and 65 were females; the mean age was (55.7±9.3) years old and 48 patients (67.6%) were less than 60 years old; the median confirmed duration of radiation rectal injury was 2.0 (1.0, 5.0) years. (1) Evaluation of symptoms of radiation rectal injury: 18 cases of mild (25.4%), 27 cases of moderate (38.0%), and 26 cases of severe (36.6%). (2) Incidence of anxiety, depression and somatic disorder: 12 patients (16.9%) without comorbidities; 59 patients (83.1%) with anxiety, depression, or somatic disorder, of whom 2 patients only had anxiety, 1 patient only had depression, 9 only had somatic disorder, 2 had anxiety plus depression, 4 had anxiety plus somatic disorder, 2 had depression plus somatic disorder, and 40 had all three symptoms. (3) correlation of radiation rectal injury grading with anxiety, depression, and somatic symptom disorder: as compared to patients in mild group and moderate group, those in severe group had higher severity of anxiety and somatic symptom disorder (Z=-2.143, P=0.032; Z=-2.045, P=0.041), while there was no statistically significant difference of depression between mild group and moderate group (Z=-1.176, P=0.240). Pearson correlation analysis revealed that radiation rectal injury symptom score was positively correlated with anxiety (r=0.300, P=0.013), depression (r=0.287, P=0.015) and somatic symptom disorder (r=0.344, P=0.003). Conclusions: The incidence of anxiety, depression, and somatic symptom disorder in patients with radiation rectal injury is extremely high. It is necessary to strengthen the diagnosis and treatment of somatic symptom disorder, so as to alleviate the symptoms of patients with pelvic perineum pain and improve the quality of life.


Asunto(s)
Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Ansiedad , Estudios Transversales , Depresión , Calidad de Vida , Recto , Encuestas y Cuestionarios
17.
Waste Manag Res ; 38(1): 27-34, 2020 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-31709930

RESUMEN

This research investigated the heavy metal leaching property and cementitious material preparation by treating municipal solid waste incineration fly ash through the molten salt process. The results indicated that the heavy metal thermal evaporation of fly ash in the molten salt was related to molten salt composition, heat treatment temperature and atmosphere. After treatment with sodium chloride molten salts (contains 10-50 wt% calcium chloride) from 900°C to 1000°C for 2 h, the leaching concentrations of lead, cadmium, copper, zinc and other heavy metals in fly ash were decreased more than 90% and they could fully meet with the landfill standard. Moreover, after molten salt treatment, the weight fraction of fly ash was reduced by 50 wt% than the original one, and the fly ash has been changed as a kind of cementitious material, which has excellent cementitious property. The X-ray diffraction result indicated that the main crystal mineral composition of cementitious materials obtained was alite, belite, alinite and calcium sulphate.


Asunto(s)
Metales Pesados , Eliminación de Residuos , Carbono , Ceniza del Carbón , Incineración , Material Particulado , Cloruro de Sodio , Residuos Sólidos
18.
Artículo en Chino | WPRIM (Pacífico Occidental) | ID: wpr-872821

RESUMEN

Objective:To investigate the effect of Huangqi Jianzhongtang on Janusprotein tyrosine kinase 2/signal transducers and transcriptional activator protein 3 (JAK2/STAT3) signal pathway in rats with spleen-stomach deficiency cold type gastric ulcer (GU). Method:A total of 60 SPF level Wistar rats were randomly divided into two groups: blank group and model group. Model rats were used to reconstruct the spleen-stomach deficiency cold type GU model by comprehensive modeling method. Model rats were divided into model group, Anweiyang group and high, medium and low-dose Huangqi Jianzhongtang groups according to the random number table, with 10 rats in each group. Rats in blank group and model group were given 10 mL·kg-1·d-1 distilled water, and 16, 8, 4 g·kg-1·d-1 Huangqi Jianzhongtang, respectively. Rats in the positive control group were given 0.14 g·kg-1·d-1 Anweiyang for 21 days. The gene expressions of JAK2 and STAT3 in the ulcer tissue were detected by Real-time fluorescent quantitative polymerase chain reaction (Real-time PCR), the protein expressions and phosphorylation levels of JAK2 and STAT3 in the ulcer tissue were detected by Western blot, and the contents of interleukin-10(IL-10)and interleukin-17(IL-17)in the gastric tissue of each group were detected by enzyme-linked immunosorbent assay (ELISA). Result:Compared with the blank group, the general survival condition of the model group was worse, the content of IL-10 in gastric homogenate was significantly reduced, while the content of IL-17 was significantly increased (P<0.05), the protein expressions of JAK2 and STAT3 in gastric tissue was not significantly increased, whereas the gene expressions and phosphorylation levels of JAK2 and STAT3 were significantly increased (P<0.05). Compared with the model group, the content of IL-10 increased, but the content of IL-17 decreased, the gene expressions of JAK2 and STAT3 and the level of protein phosphorylation decreased in the treatment group, especially in the high-dose Huangqi Jianzhongtang group, with statistically significant differences (P<0.05). Conclusion:Huangqi Jianzhongtang can improve the survival condition of rats with spleen stomach deficiency cold type gastric ulcer, and its mechanism may be related to the intervention of gastric mucosal immune barrier dysfunction mediated by JAK2/STAT3 pathway activation.

19.
Artículo en Chino | WPRIM (Pacífico Occidental) | ID: wpr-872984

RESUMEN

Objective::To investigate the effect of Bletillae Rhizoma polysaccharide on the expressions of phosphatidylinositol 3-kinase (PI3K), protein kinase B (Akt) gene protein and its mediated cytokines interleukin-2 receptor (IL-2R) and interleukin-4 (IL-4) in gastric tissue of rats with gastric ulcer (GU). Method::Sixty SPF Wistar rats were randomly divided into blank group and model group.The GU model was replicated by direct acetic acid cauterization in model group.The GU model rats were randomly divided into five groups: model group, positive control group, and large, medium and small-dose Bletillae Rhizoma polysaccharide groups, with 10 rats in each group.Rats in blank group and GU model group were given 10 mL·kg-1·d-1 distilled water by gavage, rats in large, medium and small-dose groups were given 0.5, 0.25, 0.125 g·kg-1·d-1 Bletillae Rhizoma polysaccharide by gavage, while rats in positive control group were given 0.3 g·kg-1·d-1 ranitidine by gavage for 15 days.Serum nitric oxide (NO) content, pepsinase activity and cytokines IL-2R and IL-4 levels in rats of each group were measured by enzyme-linked immunosorbent assay (ELISA), PI3K and Akt mRNA expressions were detected by Real-time fluorescent quantitative polymerase chain reaction (Real-time PCR), and PI3K and Akt protein expressions were detected by Western blot. Result::Compared with the blank group, the contents and gene expressions of cytokines IL-2R and IL-4 in gastric tissue were significantly increased, and the PI3K and Akt genes and protein expressions were significantly increased, with statistical significance (P<0.01). Compared with GU model group, the content and gene expressions of IL-2R and IL-4 in large, medium and small-dose Bletillae Rhizoma polysaccharide groups were decreased significantly, and the PI3K and Akt gene and protein expressions were decreased significantly in large-dose Bletillae Rhizoma polysaccharide group, while those in large and medium-dose Bletillae Rhizoma polysaccharide groups were decreased significantly (P<0.05, P<0.01). Conclusion::Bletillae Rhizoma polysaccharide can protect gastric mucosa by down-regulating PI3K and Akt gene and protein expressions and inhibiting abnormal secretion of cytokines IL-2R and IL-4.

20.
Artículo en Chino | WPRIM (Pacífico Occidental) | ID: wpr-873502

RESUMEN

@#Objective To analyze urine volume and dietary salt intake assessed by two 24 h urine specimens,to discuss its application value for evaluating population level and individual level dietary salt intake. Methods The subjects aged 18-69 years were selected from four counties in Shandong Province and Jiangsu Province from 2013 to 2014 by using multi-stage stratified cluster random sampling method. A questionnaire survey was conducted and two 24 h urine with an interval of one day were collected. The differences between two 24 h urine volume,and the dietary salt intake between two 24 h urine were assessed at individual level and population level. Results A total of 1 288 subjects was( 42.3± 14.0) years old,of which 626( 48.6%) were males. The average urine volume of the subjects was ( 1 462±437) ml. The first 24 h urine volume ( 1 427±488) ml was lower than the second 24 h urine volume ( 1 498± 552) ml ( t = -4.439,P<0.001) . The dietary salt intake was ( 9.8±3.3) g,and the dietary salt intake of males ( 10.1±3.5) g was higher than that of females ( 9.5±3.1) g ( t = 3.09,P= 0.002) . There was a significant difference in dietary salt intake among different age groups ( F= 7.57,P<0.001) . The dietary saltintake of 1 136 ( 88.2%) subjects was higher than the recommended level. At the individual level,the participants with the absolute difference with 1g between the subjects’two 24 h urinary salt excretion was 279 ( 21.7%) ,and the participants with the absolute difference with >3 g was 48.5%. At the population level,the first 24 h urinary salt excretions ( 9.9 ± 4.1) g was similar to that in the second 24 h urine and ( 9.7±4.0) g ( P= 0.1021) . The intraclass correlation coefficients between salt excretions in the two 24 h urine was 0.508( 95% CI: 0.451-0.559) . Conclusion The results of this study suggest that 24 h urinary salt excretion can better assess the salt intake at population level,but cannot accurately reflect the individual’s salt intake.

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