内质网应激与非酒精性脂肪性肝病肝损伤

肝脏 ›› 2023, Vol. 28 ›› Issue (6): 633-636.

内质网应激与非酒精性脂肪性肝病肝损伤

曾伟兰, 汪艳

510515 广州广东省肝纤维化工程技术研究中心,南方医科大学中心实验室,南方医科大学药学院

收稿日期:2023-03-13 出版日期:2023-06-30 发布日期:2023-08-30
通讯作者: 汪艳,Email: yanwang@smu.edu.cn
基金资助:
国家自然科学基金项目(82070589);广东省自然科学基金项目(2022A1515010218);广州市科技计划项目(202201011715)

Received:2023-03-13 Online:2023-06-30 Published:2023-08-30

摘要/Abstract

摘要： 非酒精性脂肪性肝病(NAFLD)是以肝脏脂质蓄积为主要特征的多因素疾病。脂质异常累积可造成肝细胞内质网(ER)功能涉及的蛋白平衡紊乱。当ER中未折叠或错误折叠蛋白累积时,细胞启动自身防御保护机制,出现ER应激,引起未折叠蛋白质反应(UPR),诱导蛋白质合成阻断、ER伴侣表达和错误折叠蛋白降解;这一过程主要涉及肌醇需要酶1(IRE1)、蛋白激酶R(PKR)样ER激酶(PERK)和激活转录因子6(ATF6)等信号通路的激活。值得注意的是,并非所有ER应激反应都加剧NAFLD肝损伤;轻度或中度ER应激可触发“适应性/细胞保护性”UPR,减轻NAFLD肝病理表现,恢复ER稳态;但是强烈或持续的ER应激可出现“适应不良的/不受限的/终末的”UPR,细胞启动内部凋亡机制。另外,慢性或急性ER应激也可引起不同的NAFLD肝损伤结局。因此,设计以UPR作为靶点的ER靶向递药系统,可为NAFLD治疗新药研发提供线索。

关键词: 非酒精性脂肪性肝病, 内质网应激, 未折叠蛋白反应, 肝脂肪变, 肝损伤

曾伟兰, 汪艳. 内质网应激与非酒精性脂肪性肝病肝损伤[J]. 肝脏, 2023, 28(6): 633-636.

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