铁死亡在缺血性脑卒中的作用

Roles of ferroptosis in ischemic stroke

缺血性脑卒中(ischemic cerebral strock,ICS)是一种由脑部血流不足引起的疾病,可以直接导致神经损伤,目前仍没有十分有效的神经保护剂。铁死亡是一种主要依赖于铁的脂质过氧化物驱动、受多种细胞代谢途径进行调控的细胞程序性死亡方式。铁死亡在ICS的病理生理发展中也发挥重要作用,能诱发和加重脑缺血后的损伤并贯穿着整个病理过程。ICS损伤的铁死亡机制涉及铁超载、氧化还原失调和脂质过氧化等。参与ICS的铁死亡调控的主要信号通路,包括SLC7A11-GSH-GPX4、AMPK/PGC-1α及COX-2/PGE2等。本文以铁死亡的作用机制为切入点,通过综述铁死亡与ICS之间的关系,以期为ICS的临床研究和治疗,以及寻找新的治疗靶点提供思路。

Ischemic cerebral strock(ICS)is a disease caused by insufficient blood flow to the brain,which can directly lead to nerve damage,and there are still no very effective neuroprotective agents.Ferroptosis is a form of programmed cell death that is primarily dependent on iron-dependent lipid peroxides and regulated by a variety of cellular metabolic pathways.Ferroptosis also plays an important role in the pathophysiological development of ICS,which can induce and aggravate damage after cerebral ischemia and run through the entire pathological process.The mechanism of iron death in ICS injury involves iron overload,redox imbalance,and lipid peroxidation.The main signaling pathways involved in the regulation of ferroptosis in ICS include SLC7A11-GSH-GPX4,AMPK/PGC-1α and COX-2/PGE2.This paper takes the mechanism of action of ferroptosis as the starting point,and reviews the relationship between ferroptosis and ICS,in order to provide ideas for clinical research and treatment of ICS and the search for new therapeutic targets.