褪黑素通过抑制内质网应激减轻小鼠脑缺血再灌注损伤

摘要

目的 探讨褪黑素对抗小鼠脑缺血再灌注损伤(cerebral ischemia reperfusion injury,CIRI)的作用及其机制.方法 30只雄性C57BL/6小鼠随机分为假手术组、CIRI组和褪黑素处理组(n=10),线栓法建立大脑中动脉闭塞模型.通过神经功能评分、脑水含量和脑梗死体积测定评价脑损伤程度,应用蛋白质印迹分析检测凋亡相关蛋白Bim、Bcl-2以及内质网应激相关分子C/EBP同源蛋白(C/EBP homologous protein,CHOP)表达水平.结果 与CIRI组相比,褪黑素处理组小鼠神经功能评分显著改善、脑水肿程度显著降低并且脑梗死体积显著缩小(P均＜0.05).此外,褪黑素处理组Bcl-2表达显著上调,Bim和CHOP表达显著下调(P均＜0.05).结论 褪黑素可能通过调控CHOP发挥对抗CIRI的作用,内质网应激在CIRI中扮演着重要角色.%Objective To investigate the effect of melatonin against cerebral ischemia reperfusion injury (CIRI) in mice and its mechanism.Methods Thirty male C57BL/6 mice were randomly divided into sham operation group,CIRI group,and melatonin treatment group (n =10 in each group).A middle cerebral artery occlusion model was induced by suture method.The degree of brain injury was evaluated by neurological function score,brain water content,and cerebral infarction volume.Western blot analysis was used to detect apoptosis-related proteins Bim,Bcl-2,and endoplasmic reticuhm stress-related molecules C/ EBP homologous protein (C/EBP) expression.Results Compared with the CIRI group,the neurological function score was significantly improved,the degree of cerebral edema was significantly reduced,and the volume of cerebral infarction was significantly reduced in the melatonin treatment group (all P ＜0.05).In addition,the expression of Bcl-2 was significantly up-regulated in the melatonin treatment group,and the expression of Bim and CHOP was significantly down-regulated (all P ＜ 0.05).Conclusion Melatonin may play an anti-CIRI role by regulating CHOP,and endoplasmic reticulum stress plays an important role in CIRI.