| Purpose: Resveratrol (Res) is a polyphenols. Much interest has beenfocused on Res due to its effect of cardiovascular and cerebrovascularprotection, anticarcinogenic and anti-inflammatory. But its mechanisms ofaction against cerebral ischemia are still controversial and poorly defined.This study is undertaken to focus on the effect of Res on autophagy and itspossible patheways of regulation in rats model of focal cerebralischemia-reperfusion injury and elucidate further the mechanism of Resagainst cerebral ischemia injury.Methods: Eighty-eight male SD rats were randomly divided into fourgroups:sham operation group (S group), model group (M group), low dose ofRes (15mg/kg) group (R1group) and high dose of Res (40mg/kg) group (R2group), additional3-MA (autophagy inhibitor)+R2group and Sirtinol(Sirt1inhibitor)+R2group were also used in certain analysis. The middlecerebral artery occlusion (MCAO) model was established by intraluminalsuture method. After reperfusion for24h, neurological scores were studied;Nissl’s staining was used to observe the neurons injury; The ultrastructure of neurone and the quantity changes of autophagic vacuoles were observed byusing transmission electron microscopy (TEM); Immunohistochemistry,RT-PCR and Western blotting were used to analyse the mRNA and proteinexpression of Sirtuins1(Sirt1)，microtubule-associated protein light chain3(LC3) and Beclin1, respectively; Method of2,3,5-triphenyltetrazoliumchloride (TTC) straining was used to evaluate infarct volume; Theexpression of Sirt1+LC3in brain was detected by double-labelimmunofluorescence staining in R2group and Sirtinol+R2group.Results: The neurological scores of rats treated with Res were reducedapparently compared with M group. Compared with M group, Res canincrease the density of Nissl and alleviate the pathological injury of cerebralcortical neuron. Autophagic vacuoles increased after treatment with Res.The mRNA and protein expression of Sirt1, LC3and Beclin1significantlyincreased following cerebral ischemia compared with S group, while theyfurther increased even after Res preconditioning. Besides, a greater increaseof them was observed in R2group compared to R1group. Examined by TTCstaining, the volume of cerebral infarction of rats with Ras preconditioningwere reduced, but this effect can be antagonisted by autophagy inhibitor3-methyladenine (3-MA). Double-label immunofluorescence shows thatsirtinol pretreatment can significantly inhibit the expression of Sirt1andLC3induced by Res.Conclusion: Autophagy induced by Res through Sirt1activation may involve the novel mechanism of Res in protecting against cerebralischemia-reperfusion injury. |
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