Keap1/Nrf2/ARE信号通路可通过调节氧化应激缓解脓毒症过程中的细胞铁死亡  

Kelch-like ech-associated protein 1/nuclear factor E2-related factor 2/antioxidant response element pathway alleviates ferroptosis in sepsis by regulating oxidative stress

作　　者：李嘉柔 王洪亮[1] Li Jiarou;Wang Hongliang(Department of Critical Care Medicine,the Second Affiliated Hospital of Harbin Medical University,Harbin 150086,Heilongjiang,China)

机构地区：[1]哈尔滨医科大学附属第二医院重症医学科,黑龙江哈尔滨150086

出　　处：《中华危重病急救医学》2021年第7期881-884,共4页Chinese Critical Care Medicine

基　　金：黑龙江省博士后科研启动基金(LBH-Q19137)。

摘　　要：脓毒症是感染导致机体宿主反应失调引起的危及生命的器官功能障碍,在全球有较高的发病率与病死率。脓毒症的重要特征是炎症反应,剧烈炎症反应产生的细胞因子会激活中性粒细胞,引起活性氧(ROS)的过量生成,从而造成组织器官损伤,并进一步发展为器官功能障碍和衰竭。铁死亡是近些年发现的一种铁依赖性的全新的细胞死亡方式,其主要机制为二价铁诱导的细胞内脂质过氧化与抗氧化体系〔谷胱甘肽(GSH)和谷胱甘肽过氧化物酶4(GPX4)〕表达量降低。最近众多研究表明,Kelch样环氧氯丙烷相关蛋白1/核因子E2相关因子2/抗氧化反应元件(Keap1/Nrf2/ARE)信号通路可通过改善氧化应激来缓解脓毒症过程中的细胞铁死亡。本文对Nrf2抑制脓毒症过程中细胞铁死亡的有关分子机制研究进行综述,以期为干预脓毒症进展提供预防和治疗思路。Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection,and has a high morbidity and mortality worldwide.The characteristic of sepsis is the inflammatory reaction.Cytokines produced by the severe inflammatory reaction can activate neutrophils and cause excessive production of reactive oxygen species(ROS),thus damage cells and tissue,and further develop into organ dysfunction and failure.Ferroptosis is an iron-dependent form of nonapoptotic cell death discovered recently.Its main mechanism is the intracellular lipid peroxidation induced by iron and the low expression of antioxidant systems[glutathione(GSH)and glutathione peroxidase 4(GPX4)].Recently,many studies have shown that Kelch-like ech-associated protein 1/nuclear factor E2-related factor 2/antioxidant response element(Keap1/Nrf2/ARE)signal pathway can improve oxidative stress and alleviate ferroptosis in sepsis.This article reviews the molecular mechanism and research of Nrf2 inhibiting ferroptosis in sepsis,in order to innovate prevention and treatments for the intervention of sepsis.

关 键 词：核因子E2相关因子2 脓毒症 氧化应激 铁死亡 

分 类 号：R459.7[医药卫生—急诊医学]