摘要
肝纤维化常发生于大多数慢性肝病,其直接病因是细胞外基质蛋白过度积累.铁死亡(ferroptosis)是一种铁依赖性脂质过氧化驱动的程序性细胞死亡,区别于细胞凋亡、细胞坏死、细胞焦亡的新型细胞程序性死亡方式.活性氧异常产生和铁代谢失衡是铁死亡的发生的中心环节.二价铁或酯氧合酶催化细胞膜上不饱和脂肪酸发生脂质过氧化,从而诱导细胞死亡.此外,抗氧化体系(谷胱甘肽系统)的调控核心酶谷胱甘肽过氧化物酶-4(GPX4)的降低也与铁死亡发生密切相关.近年来,多项研究表明铁死亡参与肝纤维化进程,包括p62、Keap1/NRF2、p53等信号通路.本文将围绕铁死亡相关信号通路,以及铁死亡介导的肝脏纤维化发生的机制和相应治疗策略展开综述,以期为铁死亡介导的抗肝脏纤维化治疗提供新思路.
Liver fibrosis often occurs in chronic liver diseases,and the over accumulation of extracellular matrix protein is the main pathogenic factors.Ferroptosis is a form of programmed cell death driven by iron-dependent lipid peroxidation,which is a new type of programmed cell death different from apoptosis,cell necrosis and pyroptosis.Abnormal production of reactive oxygen species and imbalance of iron metabolism are the central cause of ferroptosis.Divalent iron or ester oxygenase catalyzes lipid peroxidation of unsaturated fat acids on cell membrane,thus induce cell death.In addition,the reduction of glutathione peroxidase-4(GPX4)is also closely related to the occurrence of ferroptosis.In recent years,many studies have shown that ferroptosis is involved in the process of liver fibrosis,including p62,Keap1/NRF2,p53 and other signaling pathways.This article will focus on ferroptosis related signaling pathways,the mechanism of ferroptosis mediated liver fibrosis and the corresponding treatment strategies.It will provide new ideas for ferroptosis mediated anti liver fibrosis treatment.
作者
史云鹏
单关月
万慧
李海军
Shi Yunpeng;Shan Guanyue;Wan Hui;Li Haijun(Department of Hepatobiliary and Pancreatic Surgery,China-Japan Union of Jilin University,Changchun 130033,China;Department of Tumor Immunology,the first hospital of of Jilin University,Changchun 130023,China)
出处
《中华实验外科杂志》
CAS
北大核心
2023年第11期2412-2415,共4页
Chinese Journal of Experimental Surgery
基金
国家自然科学基金项目(81970529、82202414)
吉林省卫生科研人才专项项目(2022SC235)。
关键词
肝纤维化
铁死亡
肝星状细胞
Liver fibrosis
Ferroptosis
Hepatic stellate cells
