AIM:To investigate the mechanism by which resveratrol(Res)up-regulates the hypoxia-inducible factor-1α(HIF-1α)/BCL2-adenovirus E1B 19 kD-interacting protein 3(BNIP3)signaling pathway to induce autophagy,thereby alleviating cerebral ischemia-reperfusion injury(CIRI)in rats.METHODS:Totally 120 SD rats were randomly divided into 6 groups:sham group,CIRI group,Res group,Res+HIF-1α activator CoCl2 group,Res+HIF-1α inhibitor 2-methoxyestradiol(2ME2)group,and Res+autophagy inhibitor 3-methyladenine(3-MA)group.Twelve rats with failed surgical modeling were excluded,leaving 18 rats in each group.The rats in CIRI group,Res group,Res+CoCl2 group,Res+2ME2 group and Res+3-MA group were subjected to middle cerebral artery occlusion(MCAO)modeling using the su-ture method,with 2 h of ischemia followed by 24 h of reperfusion.The rats in sham group underwent MCAO modeling sur-gery without suture insertion.The Zea Longa modified scoring method was used to assess rat neurological behavior,TTC staining was used to measure rat cerebral infarct volume,and immunohistochemistry and immunoblotting were performed to detect the expression levels of HIF-1α,BNIP3,beclin-1 and mammalian target of rapamycin(mTOR)proteins in the rat cerebral cortex.RESULTS:Compared with CIRI group,the rats treated with Res showed significantly improved spon-taneous behavioral function and reduced cerebral infarct volume.The expression of HIF-1α,BNIP3 and beclin-1 proteins increased,while mTOR protein expression decreased in rat brain tissue.Compared with the Res group,rats treated with Res+CoCl2 showed further improvement in spontaneous behavioral function and further reduction in cerebral infarct vol-ume.The expression of HIF-1α,BNIP3 and beclin-1 proteins increased,while mTOR protein expression decreased in rat brain tissue.Rats in the Res+2ME2 and Res+3-MA groups exhibited weakened neurological function and increased cere-bral infarct volume,accompanied by decreased expression of HIF-1α,BNIP3 and beclin-1 proteins,and increased expres-sion of mTOR protein in rat brain tissue.CONCLUSION:Resveratrol may alleviate cerebral ischemia-reperfusion injury by upregulating the HIF-1α/BNIP3 pathway and subsequently activating autophagy.

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.

Objective:To explore the mechanism of pterostilbene(PTE)in preventing and treating neuroinflamma-tion after cerebral ischemia-reperfusion injury(CIRI)in rats.Methods:Ninety male SD rats were randomly divided in-to a sham group,a model group(MCAO/R),a low-dose PTE group(PTE-L),a medium-dose PTE group(PTE-M),and a high-dose PTE group(PTE-H).CIRI model was prepared by middle cerebral artery occlusion reperfusion(MCAO/R)in rats.The neurological deficit in rats was evaluated by Zea Longa score.The volume of cerebral infarc-tion was detected by TTC staining.The morphological changes of ischemic cortex was observed HE staining.The ex-pressions of cyclooxygenase-2(COX-2),prostaglandin D2 receptor(DP2)and prostaglandin D1 receptor(DP1)were detected by RT-qPCR and Western Blot.The expressions of prostaglandin D2(PGD2),interleukin-1 β(IL-1β)and tumor necrosis factor-α(TNF-α)were detected by ELISA.Results:Compared with the sham group,the MCAO/R group showed a significant increase in neurological scores(P＜0.05),a significant increase in cerebral infarction vol-ume(P＜0.05),and aggravated cortical damage in the ischemic area.Additionally,there were significant increase in the expressions of COX-2,DP2 mRNA and protein(P＜0.05),along with increased expressions of PGD2,IL-1β and TNF-α(P＜0.05).Compared with the MCAO/R group,the PTE-L,PTE-M,and PTE-H groups showed a significant decrease in neurological scores(P＜0.05),a significant decrease in cerebral infarction volume(P＜0.05),and markedly alleviated cortical damage in the ischemic region.Additionally,there were significant decrease in the expres-sions of COX-2,DP2 mRNA and protein(P＜0.05),along with decreased expressions of PGD2,IL-1β and TNF-α(P＜0.05).Furthermore,a dose-effect relationship was observed for the neuroprotective effects of PTE on brain tissue(P＜0.05).However,there were no significant differences in the expressions of DP,mRNA and protein among all groups(P＞0.05).Conclusion:PTE can attenuate the neuroinflammation of CIRI in rats by inhibiting COX-2/PGD2/DP2 signaling pathway.

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.

Objective:To explore the mechanism of pterostilbene(PTE)in preventing and treating neuroinflamma-tion after cerebral ischemia-reperfusion injury(CIRI)in rats.Methods:Ninety male SD rats were randomly divided in-to a sham group,a model group(MCAO/R),a low-dose PTE group(PTE-L),a medium-dose PTE group(PTE-M),and a high-dose PTE group(PTE-H).CIRI model was prepared by middle cerebral artery occlusion reperfusion(MCAO/R)in rats.The neurological deficit in rats was evaluated by Zea Longa score.The volume of cerebral infarc-tion was detected by TTC staining.The morphological changes of ischemic cortex was observed HE staining.The ex-pressions of cyclooxygenase-2(COX-2),prostaglandin D2 receptor(DP2)and prostaglandin D1 receptor(DP1)were detected by RT-qPCR and Western Blot.The expressions of prostaglandin D2(PGD2),interleukin-1 β(IL-1β)and tumor necrosis factor-α(TNF-α)were detected by ELISA.Results:Compared with the sham group,the MCAO/R group showed a significant increase in neurological scores(P＜0.05),a significant increase in cerebral infarction vol-ume(P＜0.05),and aggravated cortical damage in the ischemic area.Additionally,there were significant increase in the expressions of COX-2,DP2 mRNA and protein(P＜0.05),along with increased expressions of PGD2,IL-1β and TNF-α(P＜0.05).Compared with the MCAO/R group,the PTE-L,PTE-M,and PTE-H groups showed a significant decrease in neurological scores(P＜0.05),a significant decrease in cerebral infarction volume(P＜0.05),and markedly alleviated cortical damage in the ischemic region.Additionally,there were significant decrease in the expres-sions of COX-2,DP2 mRNA and protein(P＜0.05),along with decreased expressions of PGD2,IL-1β and TNF-α(P＜0.05).Furthermore,a dose-effect relationship was observed for the neuroprotective effects of PTE on brain tissue(P＜0.05).However,there were no significant differences in the expressions of DP,mRNA and protein among all groups(P＞0.05).Conclusion:PTE can attenuate the neuroinflammation of CIRI in rats by inhibiting COX-2/PGD2/DP2 signaling pathway.