UPR-ATF6通路在心搏骤停后缺血/再灌注损伤中的研究进展  

Research progress of the unfolded protein response-activating transcription factor 6 pathway in ischemia-reperfusion injury post cardiac arrest

作　　者：袁竹 陆礼萍 余追[1] Yuan Zhu;Lu Liping;Yu Zhui(Department of Critical Care Medicine,Renmin Hospital of Wuhan University,Wuhan 430060,Hubei,China)

机构地区：[1]武汉大学人民医院重症医学科,湖北武汉430060

出　　处：《中华危重病急救医学》2022年第9期999-1003,共5页Chinese Critical Care Medicine

基　　金：国家自然科学基金(81772039)。

摘　　要：心搏骤停(CA)及心肺复苏(CPR)后的缺血/再灌注(I/R)过程是导致包括心功能障碍和脑损伤在内的心搏骤停后综合征(PCAS)的重要原因。内质网中蛋白质平衡失调即内质网应激(ERS)是I/R损伤诱导的病理变化之一。未折叠蛋白反应(UPR)是细胞在ERS下触发的适应性反应。调控UPR的各分支从而缓解ERS以促进细胞存活是极具前景的治疗I/R损伤的方式。其中UPR的活化转录因子6(ATF6)信号通路的激活能通过促进内质网内蛋白平衡恢复及减少氧自由基等方式保护多种组织免受I/R损伤。本文围绕ATF6的结构和功能及其在心脏和脑I/R损伤中的作用和潜在治疗靶点等进行综述,以期为探索PCAS的有效治疗方式提供新思路。Ischemia/reperfusion(I/R)caused by cardiac arrest(CA)and subsequent cardiopulmonary resuscitation(CPR)was the primary cause of post-cardiac arrest syndrome(PCAS),including post-cardiac arrest myocardial dysfunction and post-cardiac arrest brain injury.Disturbance of endoplasmic reticulum proteostasis,so-called endoplasmic reticulum stress(ERS)was one of the pathological changes induced by I/R injury.The unfolded protein response(UPR)was an adaptive response triggered by ERS in cells.Modulating the UPR arms to alleviate ERS to promote cell survival was promising for attenuating I/R injury.Activating the activating transcription factor6(ATF6)signaling pathway,one of the arms of the UPR,confers protection against I/R injury in multiple tissues by restoring endoplasmic reticulum proteostasis and reducing oxygen free radicals.This article reviewed the structural characteristics and biological function of ATF6 and focused on its essential role in cardiac and cerebral I/R injury as well as potential therapeutic targets,hoping to provide new ideas for the effective treatment of PCAS.

关 键 词：心搏骤停 缺血/再灌注损伤 活化转录因子6 内质网应激 未折叠蛋白反应 

分 类 号：R541.78[医药卫生—心血管疾病]