白藜芦醇激活自噬抑制焦亡减轻脑缺血再灌注损伤  

Resveratrol activates autophagy and inhibits pyroptosis to alleviate cerebral ischemia-reperfusion injury

作　　者：张小良 高赛红 杨迎春 汪庆钰 贾书雨 ZHANG Xiaoliang;GAO Saihong;YANG Yingchun;WANG Qingyu;JIA Shuyu(Department of Anatomy,Fenyang College of Shanxi Medical University,Fenyang 032200,Shanxi,China;Fe-nyang College of Shanxi Medical University,Fenyang 032200,Shanxi,China)

机构地区：[1]山西医科大学汾阳学院解剖教研室,山西汾阳032200 [2]山西医科大学汾阳学院,山西汾阳032200

出　　处：《中国临床药理学与治疗学》2024年第11期1240-1248,共9页Chinese Journal of Clinical Pharmacology and Therapeutics

基　　金：吕梁市重点社会发展项目(2021SHFZ-2-102);山西医科大学汾阳学院科技扶持项目(2019C03);大学生创新创业训练项目(FDC202210)。

摘　　要：目的:研究白藜芦醇(Res)可能通过激活自噬抑制焦亡减轻脑缺血再灌注损伤(CIRI)。方法:100只SD大鼠采用线栓法制备大脑中动脉栓塞/再灌注(MCAO/I)模型,手术失败大鼠剔除,按照随机原则分为7组:假手术(Sham)组、模型对照(Model)组、白藜芦醇预处理(Res)组、3-甲基腺嘌呤(3-MA)组、白藜芦醇+3-甲基腺嘌呤(Res+3-MA)组、Z-YVAD组、Res+Z-YVAD组,每组12只。采用Longa评分、TTC染色及测量脑梗死体积评估大鼠神经功能缺损及脑损伤;免疫组化、免疫荧光及免疫印迹法检测自噬相关蛋白Beclin-1、LC3-II、P62及焦亡相关蛋白NLRP3、caspase-1、GSDMD、IL-1β的表达。结果:白藜芦醇预处理可以改善大鼠神经功能缺损,减小脑梗死体积,上调自噬相关蛋白Beclin-1、LC3-II,下调P62及焦亡相关蛋白NLRP3、caspase-1、GSDMD、IL-1β的表达。自噬抑制剂3-MA可以完全逆转Res的上述作用。加入焦亡抑制剂Z-YVAD后,自噬相关蛋白Beclin-1、LC3-II及P62变化不明显,NLRP3、caspase-1、GSDMD、IL-1β的表达明显减少,大鼠神经功能缺损加重,脑梗死体积增大。结论:Res可能通过激活自噬抑制焦亡减轻脑缺血再灌注损伤,可能与P62蛋白的调控有关。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-1βexpression.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-1βsignifi-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.

关 键 词：白黎芦醇 缺血再灌注损伤 自噬 焦亡 

分 类 号：R322.81[医药卫生—人体解剖和组织胚胎学] R965.2[医药卫生—基础医学]