铁死亡与非酒精性脂肪性肝病

Ferroptosis and Non-alcoholic fatty liver disease

铁死亡是一种不同于其他细胞死亡模式的程序性死亡方式,它的发生机制主要是因为脂质过氧化和铁失衡。现有研究已证实铁死亡与肿瘤、糖尿病、肾病等多种疾病的发生发展有关。非酒精性脂肪性肝病(NAFLD)最近被重新定义并重新分类为代谢功能障碍相关脂肪性肝病,其发病率越来越高,但是其发病机制尚不完全清楚。目前研究发现铁死亡通过谷胱甘肽过氧化物酶4(GPX4)途径、铁超载和脂质过氧化、核因子E_(2)相关因子2(Nrf2)激活、炎症等途径作用于肝脏,最终导致NAFLD的发生发展。本文回顾了铁死亡的特征以及铁死亡的发生机制,总结了铁死亡在NAFLD发病机制中的最新进展。目前已有部分研究提出采用铁死亡抑制剂治疗铁过载相关疾病,未来可能会有更多的研究探索铁死亡抑制剂对于NAFLD不同阶段的治疗作用。

Ferroptosis is a programmed cell death that is different from other cell death modes,and its mechanism is mainly due to lipid peroxidation and iron imbalance.Existing studies have confirmed that ferroptosis is related to the occurrence and development of various diseases such as cancer,diabetes,kidney disease and so on.Nonalcoholic fatty liver disease(NAFLD)has recently been redefined and reclassified as metabolic dysfunction associated fatty liver disease,and its incidence is increasing,but its pathogenesis is not fully understood.Current studies have found that ferroptosis acts on the liver through GPX4 pathway,iron overload and lipid peroxidation,Nrf2 activation,inflammation and other pathways,eventually leading to the occurrence and development of NAFLD.This article reviews the characteristics and mechanisms of ferroptosis,and summarizes the latest progress of ferroptosis in the pathogenesis of NAFLD.At present,some studies have proposed the use of ferroptosis inhibitors for the treatment of iron overloading related diseases.In the future,more studies may explore the role of ferroptosis inhibitors in the treatment of different stages of NAFLD.