SIRT1_PGC-1α Signaling Pathway In The Neuroprotection Of Limb Ischemic Postconditioning Limit Cerebral Ischemia Reperfusion Injury In Rats

Objective:Limb ischemic postconditioning(IPostC) has emerged as an innovative treatment strategy to attenuate ischemic- reperfusion injuries and improve neurological outcomes. However, the mechanisms involved have not been completely elucidated. In this study, we investigate the role of SIRT1_PGC-1α Signaling Pathway in the Neuroprotection of limb ischemic postconditioning reducing cerebral ischemia reperfusion injury in rats.Methods : Male Sprague-Dawley rats were randomly divided into four groups, sham-operated group(sham group), ischemia reperfusion group(I/R group), limb ischemia postconditioning group(LPostC group), and limb ischemia postconditioning group + inhibitor of SIRT1group(EX-527 group). The ischemia and reperfusion injury model was introducing by embolism line methods. To set up LPost C model three cycles of occlusion and non-occlusion for the bilateral femoral arteries to make the limb ischemia post-conditioning. For EX-527 Model, EX-527 was injected into lateral ventricle 48 hours before introducing cerebral ischemia-reperfusion model. Other groups were given intraperitoneal dose of 25% DMSO as control. After 24 h reperfusion, Groups of neurologic tests and analysis were recorded.Post-test cerebral infarction volume was measured by TTC. Neuron apoptosis was detected by TUNEL. SOD activity and MDA content were measured by spectrophotometer. Expression of SIRT1 and PGC-1α were confirmed by Western blot. Results: Compered with the sham group, ischemia reperfusion group has the defect nerve function, SOD activity receded and MDA content increased, and the down-expression of SIRT and PGC-1α. While limb ischemia postconditioning can limit cerebral IRI, which mainly reflected in ameliorating the neurological function, diminishing the cerebral infarct volume, enhancing cell survival, SOD activity increasing and MDA content reducing, upgrading SIRT1 and PGC-1α protein(P < 0.05). After the treatment of inhibitor of SIRT1 resulted in significantly enlarge cerebral infarction volume, aggravated neuronal apoptosis, SOD activity attenuated and MDA content increased, and the down-regulation of SIRT and PGC-1α in comparison with LPostC group(P < 0.05). Conclusions: Limb ischemia postconditioning plays a role to prevent reperfusion injury following cerebral ischemia. The mechanism may be related to activate and upgrade the SIRT1_PGC- 1α signaling pathways and enhanced its ability to resist oxidative stress.