Resveratrol alleviates cerebral ischemia-reperfusion injury in rats by ac-tivating autophagy via up-regulation of HIF-1α/BNIP3 pathway
10.3969/j.issn.1000-4718.2024.07.013
- VernacularTitle:白藜芦醇通过上调HIF-1α/BNIP3通路诱导自噬而减轻大鼠脑缺血再灌注损伤
- Author:
Xiaoliang ZHANG
1
;
Saihong GAO
;
Yingchun YANG
;
Jingxiao ZHANG
Author Information
1. 山西医科大学汾阳学院解剖教研室,山西 汾阳 032200
- Keywords:
resveratrol;
ischemia-reperfusion injury;
hypoxia-inducible factor-1α;
autophagy
- From:
Chinese Journal of Pathophysiology
2024;40(7):1253-1260
- CountryChina
- Language:Chinese
-
Abstract:
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.
