Resveratrol activates autophagy and inhibits pyroptosis to alleviate cerebral ischemia-reperfusion injury
AIM:To investigate the potential of resveratrol(Res)to alleviate cerebral ischemia-re-perfusion injury(CIRI)by activating autophagy.METHODS:One hundred SD rats were purchased and subjected to middle cerebral artery occlusion/reperfusion(MCAO/R)using the suture method.Rats with failed surgeries were excluded,and they were randomly divided into seven groups:Sham(S)group,Model(M)group,Resveratrol pretreatment(Res)group,3-methyladenine(3-MA)group,Resve-ratrol+3-methyladenine(Res+3-MA)group,Z-YVAD group,and Res+Z-YVAD group,with 12 rats in each group.Neurological deficits and brain dam-age were assessed using Longa scoring,TTC stain-ing,and measurement of infarct volume.Immuno-histochemistry,immunofluorescence,and immu-noblotting were employed to detect the expression of autophagy-related proteins Beclin-1,LC3-Ⅱ,P62,and pyroptosis-related proteins NLRP3,caspase-1,GSDMD,IL-1β.RESULTS:Resveratrol pretreatment improved neurological deficits and reduced infarct volume in rats.It upregulated autophagy-related proteins Beclin-1,LC3-Ⅱ,downregulated P62,and pyroptosis-related proteins NLRP3,caspase-1,GSD-MD,IL-1β expression.The autophagy inhibitor 3-MA completely reversed the above effects of Res.After adding the pyroptosis inhibitor Z-YVAD,the changes in autophagy-related proteins Beclin-1,LC3-Ⅱ,and P62 were not significant,while the ex-pression of NLRP3,caspase-1,GSDMD,IL-1β signifi-cantly decreased.Neurological deficits worsened,and infarct volume increased in rats.CONCLUSION:Res attenuates cerebral ischemia-reperfusion injury by activating autophagy and inhibiting pyroptosis,possibly through the regulation of the P62.
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