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非凋亡程序性细胞死亡在代谢相关脂肪性肝病中的作用
陈奕婷,王培*
0
(海军军医大学(第二军医大学)药学系, 上海 200433
*通信作者)
摘要:
既往认为程序性细胞死亡就是指凋亡,因此代谢相关脂肪性肝病中肝细胞死亡的最重要原因也被默认为凋亡。随着越来越多非调亡程序性细胞死亡(铁死亡、坏死性凋亡、焦亡等)的发现,它们与炎症、活性氧、免疫信号活化高度相关的特征日益受到重视。大量证据表明,相较于“免疫沉默”的凋亡,非凋亡程序性细胞死亡似乎在代谢相关脂肪性肝病的肝细胞死亡中起到更为关键的作用,焦亡的特点是在肝脏组织中诱导大量炎症分子释放,坏死性凋亡的特点是导致肝细胞彻底坏死,铁死亡的特点则是出现较为剧烈的脂质氧化应激。本文旨在阐述非凋亡程序性细胞死亡与代谢相关脂肪性肝病的联系,并对它们在代谢相关脂肪性肝病中的可能作用机制进行探讨。
关键词:  程序性细胞死亡  代谢相关脂肪性肝病  细胞焦亡  坏死性凋亡  铁死亡  细胞凋亡  炎症
DOI:10.16781/j.CN31-2187/R.20220745
投稿时间:2022-09-21修订日期:2022-12-15
基金项目:国家自然科学基金面上项目(82073915).
Roles of non-apoptotic programmed cell death in metabolic-associated fatty liver disease
CHEN Yi-ting,WANG Pei*
(School of Pharmacy, Naval Medical University(Second Military Medical University), Shanghai 200433, China
*Corresponding author)
Abstract:
Traditionally, programmed cell death (PCD) refers to apoptosis. As such, apoptosis is considered to be the most important cause of hepatocyte death in metabolic-associated fatty liver disease (MAFLD). However, with the discovery of more and more non-apoptotic PCD (including ferroptosis, necroptosis, and pyroptosis), their characteristics which are highly related to inflammation, reactive oxygen species, and immune signal activation have been increasingly valued. A large amount of evidence shows that compared with “immune silence” apoptosis, the non-apoptotic PCD seems to play more critical roles in causing hepatocyte death in MAFLD. The characteristic of pyroptosis is to induce the release of a large number of inflammatory molecules in liver tissue, the characteristic of necroptosis is to lead to complete necrosis of liver cells, and the characteristic of ferroptosis is to have more intense lipid oxidative stress. The purpose of this article is to elaborate the relationship between non-apoptotic PCD and MAFLD, and discuss their possible interaction mechanisms in MAFLD.
Key words:  programmed cell death  metabolic-associated fatty liver disease  pyroptosis  necroptosis  ferroptosis  apoptosis  inflammation