黄芪甲苷通过调控Caspase-1介导的经典焦亡途径抑制细胞焦亡缓解脑缺血/再灌注损伤的研究

Astragaloside Ⅳ improves cerebral ischemia/reperfusion injury by inhibitingpyroptosis via regulating Caspase-1-mediated classical pyroptosis pathway

目的:探讨黄芪甲苷对缺血/再灌注(I/R)损伤脑组织的干预作用及对Caspase-1信号通路介导的细胞焦亡的影响。方法:将SD大鼠随机分为4组,分别为假手术组(Sham)、模型组(MCAO/R)、溶剂对照组(DMSO)和黄芪甲苷组(AS-Ⅳ)。大脑中动脉阻塞2 h、再灌注24 h构建大鼠脑I/R损伤模型。大鼠神经功能缺损情况采用Zea Longa评分评估,脑梗死体积采用TTC染色法进行观察,脑组织病理损伤采用HE染色法分析,采用Caspase-1和TUNEL免疫荧光双染色法观察脑组织细胞焦亡,Western blot分析脑组织内NLRP3、Cleaved Caspase-1、IL-18、IL-1β等通路蛋白表达。结果:通过构建大脑MCAO/R模型发现,黄芪甲苷可有效改善脑I/R损伤大鼠神经功能,缩小脑梗死体积,缓解梗死侧神经细胞的坏死、丢失情况,并通过调控Caspase-1介导的经典焦亡途径抑制细胞焦亡。结论:黄芪甲苷可能通过调控Caspase-1介导的经典焦亡途径抑制神经细胞焦亡,缓解脑I/R损伤。

Objective:To investigate the effect of astragalosideⅣon cerebral tissue injury caused by ischemia/reperfusion(I/R)and pyroptosis mediated by Caspase-1 signaling pathway.Methods:SD rats were randomly divided into 4 groups of sham operation(Sham),model(MCAO/R),solvent control(DMSO)and astragaloside IV(ASⅣ).Cerebral I/R injury model was established by occlusion of the middle cerebral artery for 2 hours and reperfusion for 24 hours.Zea Longa score was used to observe the neurological deficit of rats,the volume of cerebral infarction in rats was evaluate by TTC staining,pathological changes of brain tissue was observed by HE staining,pyroptosis of brain was observed by Caspase-1 and TUNEL immunofluorescence double staining,and protein expres-sions of NLRP3,Cleaved Caspase-1,IL-18 and IL-1βin brain tissue were detected by Western blot.Results:By constructing the MCAO/R model,our findings suggest that astragalosideⅣcan reduce the neurological deficit caused by I/R in rats,reduce the infarct volume ofbrain,relieve the necrosis and loss of nerve cells on the infarct side,and inhibit pyroptosis by regulating the classical pyrop-tosis pathway mediated by Caspase-1.Conclusion:AstragalosideⅣmay alleviate cerebral I/R injury by inhibiting pyroptosis via regu-lating the classical pyroptosis pathway mediated by Caspase-1.