Yuan Zhu, Lu Liping, Yu Zhui
Department of Critical Care Medicine, Renmin Hospital of Wuhan University, Wuhan 430060, Hubei, China. Corresponding author: Yu Zhui, Email:
Zhonghua Wei Zhong Bing Ji Jiu Yi Xue. 2022 Sep;34(9):999-1003. doi: 10.3760/cma.j.cn121430-20220428-00430.
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.
心脏骤停（CA）及随后的心肺复苏（CPR）所导致的缺血/再灌注（I/R）是心脏骤停后综合征（PCAS）的主要原因，PCAS包括心脏骤停后心肌功能障碍和心脏骤停后脑损伤。内质网蛋白质稳态紊乱，即所谓的内质网应激（ERS）是I/R损伤诱导的病理变化之一。未折叠蛋白反应（UPR）是细胞中由ERS触发的一种适应性反应。调节UPR分支以减轻ERS从而促进细胞存活，对于减轻I/R损伤具有前景。激活UPR分支之一的激活转录因子6（ATF6）信号通路，通过恢复内质网蛋白质稳态和减少氧自由基，对多种组织的I/R损伤具有保护作用。本文综述了ATF6的结构特征和生物学功能，并重点阐述了其在心脏和脑I/R损伤中的重要作用以及潜在治疗靶点，希望为PCAS的有效治疗提供新思路。
