非酒精性脂肪肝病中线粒体功能紊乱及其治疗策略  

Mitochondrial dysfunction in non-alcoholic fatty liver disease and its therapeutic strategies

作　　者：雷蕾 彭宗根[1] LEI Lei;PENG Zong-gen(Institute of Medicinal Biotechnology,Chinese Academy of Medical Sciences&Peking Union Medical College,Beijing 100050,China)

机构地区：[1]中国医学科学院北京协和医学院医药生物技术研究所,北京100050

出　　处：《中国新药杂志》2021年第24期2268-2275,共8页Chinese Journal of New Drugs

基　　金：国家重大新药创制科技重大专项资助项目(2018ZX09711001-003-010);中国医学科学院医学与健康科技创新工程课题资助项目(2017-I2M-3-012)。

摘　　要：非酒精性脂肪肝病(NAFLD)是一种与代谢紊乱密切相关的肝脏疾病,最主要的特征之一是肝脏线粒体功能紊乱,可导致单纯的肝脂肪变性或发展为脂肪性肝炎,甚至出现肝纤维化,最终可能导致肝硬化和肝癌发生。但目前临床上尚无针对NAFLD病因的特效治疗药物。近年来的研究发现线粒体功能紊乱与其超微结构损伤、线粒体DNA缺失、活性氧过度产生、异常的脂肪酸氧化、线粒体自噬、凋亡以及信号转导等相关。本文综述了线粒体功能紊乱在NAFLD进展中的表现、作用及其发生机制,并基于对线粒体功能紊乱的理解进一步探讨NAFLD的治疗策略,为研发防治NAFLD的创新药物提供新思路。Non-alcoholic fatty liver disease(NAFLD)is a liver disease closely related to metabolic syndrome.Hepatic mitochondrial dysfunction,as one of the most important features of NAFLD,leads to simple liver steatosis or progresses to steatohepatitis,and even liver fibrosis,which may eventually induce cirrhosis and hepatocellular carcinoma.However,there is no specific drug for the treatment of NAFLD in clinic.Recent studies found that mitochondrial dysfunction is related to ultrastructural damage,mitochondrial DNA depletion,excessive production of reactive oxygen species,and abnormities of fatty acid oxidation,mitochondrial autophagy,apoptosis,signal transduction.This article reviewed the performance,role,and mechanism of mitochondrial dysfunction in the progression of NAFLD and discussed the therapeutic strategies of NAFLD based on the understanding of mitochondrial dysfunction in NAFLD,providing new ideas for the development of innovative drugs for the prevention and treatment of NAFLD.

关 键 词：非酒精性脂肪肝 线粒体 功能紊乱 治疗药物 

分 类 号：R966[医药卫生—药理学]