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BACKGROUND:It has been shown that in a mouse model of acute traumatic brain injury,the transcriptional and translational levels of silent information regulator 1(SIRT1)activated by drugs significantly elevates the expression of SIRT1 in brain tissue,reduces inflammatory and oxidative stress in brain tissue,and improves neurological function. OBJECTIVE:To investigate the mechanism of intraperitoneal injection of SRT1720,an activator of SIRT1,to alleviate acute traumatic brain injury in rats. METHODS:Ninety Sprague-Dawley rats were randomized into three groups(n=30 per group):a sham group(without modeling),a model group and an activator group.Animal models of acute traumatic brain injury were established in the latter two groups.At 6 hours after modeling,the sham,model and activator groups were injected intraperitoneally with dimethyl sulfoxide solution,methylsulfoxide solution and SRT1720 once a day for 28 days,respectively.The time points for sampling were set,and rats'neurological function,brain tissue water content,brain tissue oxidative stress and inflammatory response,brain tissue morphology,apoptosis and angiogenesis,and the protein expression of SIRT1 in brain tissue were detected and measured. RESULTS AND CONCLUSION:Compared with the sham group,the modified neurological deficit score,brain tissue water content and apoptosis rate of rats were increased in the model group at 7,14 and 28 days of injection(P<0.05);compared with the model group,the modified neurological deficit score,brain tissue water content and apoptosis rate of rats were decreased in the activator group(P<0.05).Compared with the sham group,the levels of reactive oxygen radicals and myeloperoxidase in the brain tissue were increased(P<0.05),the levels of malondialdehyde,tumor necrosis factor α and interleukin 6 in the serum were increased(P<0.05),and the levels of superoxide dismutase in the serum were decreased in the model group at 7,14 and 28 days of injection(P<0.05).Compared with the model group,the levels of reactive oxygen radicals and myeloperoxidase in the brain tissue were decreased(P<0.05),the levels of malondialdehyde,tumor necrosis factor α and interleukin 6 in the serum were decreased(P<0.05),and the levels of superoxide dismutase in the serum were increased in the activator group at 7,14 and 28 days of injection(P<0.05).Immunohistochemical staining at 7,14 and 28 days of injection showed that the number of new vessels in the brain tissue was higher in the model group than the sham group(P<0.05)as well as higher in the activator group than the model group(P<0.05).Western blot assay indicated that at 7,14 and 28 days of injection,the expression of SIRT1 protein in the brain tissue was lower in the model group than the sham group(P<0.05)and higher in the activator group than the model group(P<0.05).Hematoxylin-eosin staining showed that at 7,14 and 28 days of injection,the degree of brain injury in the activator group was less than that in the model group.To conclude,intraperitoneal injection of the SIRT1 signal activator SRT1720 can significantly reduce oxidative and inflammatory stress in the brain tissue,inhibit neuronal apoptosis,promote angiogenesis,and alleviate brain injury in rats with acute traumatic brain injury.
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Objective To investigate the effect of a novel lymphotoxin with selectively binding to p55 tumor necrosis factor receptor (p55TNFR) on myocardial ischemia-reperfusion injury in rats in order to explore the mechanism.Methods A total of 40 SD rats were randomly (random number) assigned into four groups (n =10 in each),namely sham operation group (group A),I/R group (group B),wild type rhLTα treatment group (group C),and p55TNFR selective rhLTα (rhLTα-Q107E) treatment group (group D).After I/R model rats were established,various therapeutic agents or saline were given by continuous intravenous infusion for 24 h via a micropump.After 24 hours of treatment,serum myocardial zymogram,such as aspartate aminotransferase (AST),lactate dehydrogenase (LDH) and creatine kinase (CK),as well as superoxide dismutase (SOD),malondialdehyde (MDA) and glutathione peroxidase (GSH-Px) activities were determined.Myocardial infarction size (MIS) was measured by nitro blue tetrazolium chloride (NBT) staining.Results Compared to sham operation group,MIS,AST,LDH,CK,MDA were increased,while the activities of SOD and GSH-Px were decreased.However,all the effects were significantly reversed by treatment with rhLTα-Q107E (P ＜ 0.05) but not rhLTα (P ＞ 0.05).Conclusions The rhLTα-Q107E plays a role in the protection against myocardial ischemia-reperfusion injury in rats by the mechanism of scavenging oxygen free radicals and increasing the activity of endogenous antioxidant system.
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Objective To retrospectively analyze management of chronic lateral ankle instability and evaluate its clinical results. Methods There were 74 patients including 43 males and 31 females at age range of 15-63 years (mean 39 years). All patients had at least half year of disease history, more than twice repeated strains and over six weeks of conservative management. Of all, 41 patients were trea-ted with surgical operations including modified Brostrom in 12 patients, Myerson in eight and Chrisman-Snook in 21. The aasoeiated pathological problems should be treated at the same time, ie, tenedesis for the peroneal tendon subluxations in six patients, Achilles tendon lengthening in nine, lateral shift of cal-caneal osteotomies in eight and clearance and holes-making for the osteochondral lesions in 13. Results Of all, functional instability was alleviated in 21 patients through conservative treatment before surgery. Of 53 patients with either functional or mechanical instability, 10 patients showed symptomatic relief, two refused surgical operation and the remained 41 patients were treated surgically. Thirty-nine patients trea-ted surgically and 28 treated conservatively were followed up for 6-91 months. The Roos Functional Out-come Score was used for validating the results. The average value of the ankle functional outcome was 86.24 and 97.34 respectively following operation and conservative management. Conclusions The full examination is needed to remove any possible pathological factors for the patients with chronic lateral ankle instability. The surgical operation can obtain satisfactory functional recovery of the ankle if the conserva-tive management is failed.