RESUMEN
OBJECTIVE@#To examine the expressions of hypoxia inducible factor-1α (HIF-1α) and vascular endothelial growth factor (VEGF) in the kidney of rats with diabetic nephropathy before and after the treatment of Cordyceps sinensis, and to explore the mechanism of Cordyceps sinensis against hypoxia.@*METHODS@#The diabetes model was produced by intraperitoneal injection of 60 mg/kg streptozotocin, then the rats whose 24 h urine protein level was above 30 mg/d were thought to have suffered diabetic nephropathy. Thirty rats were randomly divided into a diabetic nephropathy group (DN group, n=15) and a Cordyceps sinensis group (CS group, n=15), and another 15 normal rats served as a normal control group (NC group, n=15). The CS group were intragastrically administered Cordyceps sinensis extract liquid [5.0 g/(kg.d)], the other groups were intragastrically administered drinking water of equal volume. Five rats in each group were killed after 2, 4, and 6 weeks. The 24 h urine protein excretion, urine β-N-acetyl glucosaminidase (NAGase) and serum creatinine were measured; the renal pathological changes were evaluated by HE and Masson staining; the mRNA and protein expressions of HIF-1α and VEGF were dectected by reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemistry.@*RESULTS@#Compared with the normal control group, the renal tubular vacuolar degeneration was obvious, and the glomerular mesangial matrix increased in the DN group. The 24 h urinary protein excretion, urine NAGase and serum creatinine also increased significantly (all P0.05).@*CONCLUSION@#The expressions of HIF-1α and VEGF increase in the kidney of rats with diabetic nephropathy, and the positive correlation suggests that there is chronic hypoxia in the renal tissue of diabetic nephropathy. Cordyceps sinensis may protect against chronic hypoxia injury in diabetic nephropathy by lowering the expressions of HIF-1α and VEGF.
Asunto(s)
Animales , Masculino , Ratas , Cordyceps , Química , Diabetes Mellitus Experimental , Metabolismo , Nefropatías Diabéticas , Metabolismo , Medicamentos Herbarios Chinos , Farmacología , Subunidad alfa del Factor 1 Inducible por Hipoxia , Genética , Metabolismo , Riñón , Metabolismo , Ratas Wistar , Factor A de Crecimiento Endotelial Vascular , Genética , MetabolismoRESUMEN
BACKGROUND/AIMS: Anticoagulation in hemodialysis (HD) patients at high risk of bleeding remains an intractable problem. Simulating endothelial cells by releasing anticoagulant on the membrane may be a promising alternative. METHODS: We modified a polyacrylonitrile (PAN) dialyzer by loading argatroban into its membrane and verified its anticoagulation efficiency and its influence on coagulation markers such as activated partial thromboplastin time (aPTT), D-dimer and thrombin-antithrombin complex (TAT) in an animal HD model. RESULTS: All HD sessions with the argatroban dialyzer were completed successfully with either no or minimal fiber clotting. D-dimer was lower in the argatroban group than in the PAN group; TAT and aPTT values were similar in the two groups, which suggests better anticoagulation and a similar influence on the coagulation system. CONCLUSION: HD with the argatroban dialyzer is feasible, safe and simple, and could be used in patients at high risk of bleeding.
Asunto(s)
Anticoagulantes/uso terapéutico , Coagulación Sanguínea/efectos de los fármacos , Ácidos Pipecólicos/uso terapéutico , Diálisis Renal/métodos , Resinas Acrílicas/química , Animales , Antitrombina III/metabolismo , Arginina/análogos & derivados , Perros , Productos de Degradación de Fibrina-Fibrinógeno/metabolismo , Masculino , Membranas Artificiales , Tiempo de Tromboplastina Parcial , Péptido Hidrolasas/metabolismo , SulfonamidasRESUMEN
BACKGROUND/AIMS: Klotho, a newly identified antiaging gene, predominantly detected in the kidney, has pleiotropic protective effects on kidney diseases. Several studies have confirmed the association between Klotho and oxidative stress. The present studies were performed to explore effects of fosinopril (Fos) and losartan (Los) on Klotho and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase expression in kidneys of spontaneously hypertensive rats (SHR). METHODS: Twenty-four male 22-week-old SHR were randomly divided into three groups: model group, Fos group and Los group. Wistar-Kyoto rats were taken as control. After 8 weeks, urinary N-acetyl-ß-D-glucosaminidase (NAGase), 24 h urinary protein (Upro), serum creatinine (Scr), blood urea nitrogen (BUN) and renal pathological changes were detected. Renal mRNA and protein expression of Klotho and three subunits of NADPH oxidase protein expression were evaluated. RESULTS: As compared to the model group, NAGase, Upro, Scr and BUN were decreased; the typical renal pathological damage was relieved in the Fos or Los group. Fos or Los inhibited the reduction of Klotho expression, and reduced the elevation of NADPH oxidase expression. CONCLUSION: Abnormal expression of Klotho and NADPH oxidase plays important roles in progression of hypertensive renal damage. Fos and Los can increase Klotho expression, and inhibit NADPH oxidase expression, which may be one of the mechanisms of their protective effects in hypertensive renal damage.
Asunto(s)
Fosinopril/farmacología , Regulación Enzimológica de la Expresión Génica , Glucuronidasa/biosíntesis , Hipertensión/enzimología , Riñón/enzimología , Losartán/farmacología , NADPH Oxidasas/biosíntesis , Animales , Progresión de la Enfermedad , Fosinopril/uso terapéutico , Glucuronidasa/genética , Hipertensión/tratamiento farmacológico , Hipertensión/genética , Riñón/efectos de los fármacos , Riñón/patología , Proteínas Klotho , Losartán/uso terapéutico , Masculino , NADPH Oxidasas/genética , ARN Mensajero/biosíntesis , Distribución Aleatoria , Ratas , Ratas Endogámicas SHR , Ratas Endogámicas WKYRESUMEN
UNLABELLED: This study aims to investigate the role of Notch pathway in the renal ischemia/reperfusion injury (IRI)-associated inflammation and apoptosis. MATERIALS AND METHODS: Male Sprague-Dawley rats were divided into three groups: normal saline (NS)-treated sham rats, NS-treated ischemia/reperfusion (I/R) rats, and N-[N-(3,5-difluorophenacetyl-l-alanyl)]-S-phenylglycine t-butyl ester (DAPT) (a γ-secretase inhibitor) treated I/R rats. I/R rat model underwent nephrectomy of the right kidney and was subjected to 60 min of left renal pedicle occlusion followed by 24 h, 48 h, and 72 h of reperfusion, respectively. The levels of creatinine, urea nitrogen (BUN), interleukin (IL)-6, tumor necrosis factor (TNF)-α in serum samples and urinary N-acety-ß-d-glucosaminidase (NAG) were assayed. Histological examinations were performed. The protein expression of Notch2, hairy/enhancer of split 1 (hes-1), NF-κB2, monocyte chemoattractant protein (MCP)-1, B-cell lymphoma 2 (bcl-2), and bcl-2-associated X (bax) were detected and the degree of apoptosis of tubular cells was evaluated. RESULTS: Renal IR induced severe tubular damage, caused significant increases in the Scr, BUN, IL-6, TNF-α, urinary NAG, Notch2, hes-1, NF-κB2, MCP-1, ratio of tubule cells apoptosis, and reduction in the ratio of bcl-2 to bax. However, DAPT treatment significantly reduced the level of Scr, BUN, IL-6, TNF-α, and NAG. Thus, I/R activates Notch2/hes-1 signaling and DAPT treatment can ameliorate the severity of tubular damage after renal IRI, lower the expression of NF-κB2, MCP-1, and bax protein, increase the expression of bcl-2 protein, and reduce the ratio of terminal 2-deoxyuridine 5-triphosphate nick end-labeling-positive cells. CONCLUSION: Notch signaling plays an important role in the renal IRI-associated inflammation and apoptosis. DAPT can protect against IRI through partly suppressing inflammation and apoptosis, which could constitute a new target for AKI.
Asunto(s)
Lesión Renal Aguda/metabolismo , Secretasas de la Proteína Precursora del Amiloide/metabolismo , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/metabolismo , Proteínas de Homeodominio/metabolismo , Receptor Notch2/metabolismo , Daño por Reperfusión/metabolismo , Lesión Renal Aguda/patología , Lesión Renal Aguda/prevención & control , Secretasas de la Proteína Precursora del Amiloide/antagonistas & inhibidores , Animales , Apoptosis/efectos de los fármacos , Citocinas/metabolismo , Dipéptidos/farmacología , Dipéptidos/uso terapéutico , Células Epiteliales/efectos de los fármacos , Etiquetado Corte-Fin in Situ , Inflamación/tratamiento farmacológico , Inflamación/metabolismo , Riñón/efectos de los fármacos , Riñón/patología , Pruebas de Función Renal , Masculino , FN-kappa B/metabolismo , Ratas , Ratas Sprague-Dawley , Daño por Reperfusión/patología , Daño por Reperfusión/prevención & control , Transducción de Señal , Factor de Transcripción HES-1 , Proteína X Asociada a bcl-2/metabolismoRESUMEN
Tumor necrosis factor (TNF)-like weak inducer of apoptosis (TWEAK) is a recently identified proinflammatory cytokine of the TNF superfamily. Studies have indicated that TWEAK plays an important role in renal, vascular injury and immune disease. The aim of this study was to explore the expression of the TWEAK in peripheral blood mononuclear cells (PBMCs) and analyze the correlation between TWEAK and disease activity and renal damage of SLE. The expression of TWEAK in PBMCs was determined by RT-PCR and western blot. SLE disease activity was evaluated by Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) 2000 score. Next were analyzed the correlations of TWEAK mRNA and protein to serum IL-10, MCP-1 and some laboratory parameters of SLE disease activity. Subjects comprised 48 patients with SLE including 25 patients with renal damage and 23 without, 20 patients with rheumatoid arthrithis (RA) and 15 healthy controls. The results showed that TWEAK expressions in PBMCs from SLE patients were significantly higher than that in RA patients or healthy controls, especially higher in those patients with renal disease. Elevated production of TWEAK is correlated positively and significantly with SLEDAI, proteinuria, serum anti-dsDNA, IL-10 and MCP-1, but inversely associated with serum complements. Our results suggested that TWEAK in PBMCs is positively related to SLE disease activity and might be involved in the pathogenesis of SLE.