| Background:Ischemic cerebrovascular disease is a serious hazard to human health of common and frequently occurring. Cerebral ischemia injury to brain cells is extremely complex pathological process, the pathogenesis involves a series of ischemic cascade reactions which includes brain energy metabolism disorders, intracellular calcium overload, toxicity of excitatory amino acid, inflammatory responses, oxidative stress, apoptosis-related genes activation and so on. These reactions are interrelated and reinforce each other, eventually leading to cell death. Oxidative stress is the core of the pathological aspects of ischemic brain injury, neuronal apoptosis after ischemic brain injury is an important form of cell death. Early neuroprotective treatment, blocking oxidative stress and apoptosis is the key to treatment. But so far, there has been no clinically significant effect recognized the neuroprotective agent was born. Therefore, to explore the clinical effective neuroprotective agents will have great significance.Resveratrol is a polyphenolic compounds that is widely present in Polygonum, Cassia, Grapes and Peanuts. That has scavenging free radicals, antioxidation, anti-inflammatory and other pharmacological activities, and low side effects. Recent results show that Resveratrol has significant protective effect on the nervous system, but the underlying mechanisms remains elusive.Objective: To investigate the protective effect of Resveratrol on cerebral ischemia / reperfusion injury and its possible mechanism.Methods: Part one: The middle cerebral artery occlusion (MCAO) model in rats was established by intraluminal thread block for 2h and reperfusion thereafter. Rats were divided randomly into sham operation group (Sham group), ischemia/reperfusion group (I/R group), low dose of Resveratrol (15 mg/kg, I/Rï¹¢R1 group) and high dose of Resveratrol (30 mg/kg, I/Rï¹¢R2 group). After 24 h reperfusion, neurological score of all groups were evaluated, infarct volume was measured by 2,3,5-triphenyltetrazolium chloride (TTC)staining,content of water in brain tissue was measured by wet and dry weight method,and pathological changes of brain tissue were observed by HE staining to evaluate neuroprotection effect of Resveratrol on cerebral ischemia/reperfusion injury. Part two: After 2 h,6 h,24 h reperfusion, content of MDA in brain tissue was detected by the chemical colorimetric, RT-PCR and western blot analysed mRNA and protein expression of nuclear factor erythroid 2-related factor 2(Nrf2) and heme oxygenase-1(HO-1). Part three: After 24 h reperfusion, TUNEL was used to measure cell apoptosis. Immunohistochemistry and western blot were used to analyse the protein expression of Caspase-3.Results: Part one: Compared with I/R group, Resveratrol pretreatment significantly ameliorated neurological scores (P<0.01), reduced infarct volume and brain water content (P<0.01), HE staining also showed that Resveratrol significantly improved neuronal injury. Part two:Compared with I/R group, Resveratrol pretreatment significantly decreased the contents of MDA in brain tissue (P<0.01), significantly upregulated the protein and mRNA expression of both Nrf2 and HO-1 (P<0.05). Part three: Compared with I/R group, Resveratrol pretreatment significantly reduced the protein expression of Caspase-3 and the number of apoptotic cells (P<0.01).Conclusion : 1. Resveratrol shows protective effects on cerebral ischemia /reperfusion injury on rats. 2. The mechanism of neuroprotective effects of Resveratrol on focal cerebral ischemia/reperfusion injury may involve the activation Nrf2/ARE signaling pathway and thus the enhanced expression of antioxidant HO-1. 3. Resveratrol can inhibit neuronal apoptosis in rats following focal cerebral ischemia/reperfusion, the mechanism may be related to downregulationed the protein expression of Caspase-3.
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