线粒体损伤介导的药源性脏器损伤评价模型研究进展  

Research Progress on Evaluation Model of Drug-induced Organ Damage Mediated by Mitochondrial Damage

作　　者：魏桂林 何青青 金强 杨凌 WEI Guilin;HE Qingqing;JIN Qiang;YANG Ling(Institute of Interdisciplinary Integrative Medicine Research,Shanghai University of Traditional Chinese Medicine,Shanghai 201203,China)

机构地区：[1]上海中医药大学交叉科学研究院,上海201203

出　　处：《世界中医药》2020年第23期3523-3535,共13页World Chinese Medicine

基　　金：国家重点研发计划项目(2017YFC1702000,2020YFC0845400);国家重大专项“重大新药创制”(2018ZX09731016-004);国家自然科学基金项目(81803489,81703604,81903576,81773810)。

摘　　要：线粒体是细胞的能量工厂,同时线粒体还参与细胞分化、维持细胞内环境平衡、细胞信息传递和调节细胞凋亡等过程。线粒体受到核DNA和线粒体DNA的双重调控,使得线粒体对于各种外源及内源性毒性物质更加敏感。药物破坏线粒体结构与功能可导致细胞坏死或凋亡。近年来研究发现多种脏器细胞线粒体是药物毒性作用的主要靶标之一,药物可通过多种途径致线粒体毒性,线粒体损伤是许多药物器官毒性反应早期的重要特征。本文主要综述常见的诱导不同器官线粒体毒性的临床药物并简要探讨药物介导线粒体毒性的机制。此外,我们还将重点讨论目前常用的线粒体毒性评价模型和评价技术,以期为预防和诊断药源性器官损伤提供思路。Mitochondria are the energy factories of cells.Meanwhile,mitochondria are also involved in processes such as cell differentiation,maintenance of the intracellular homeostasis,cell information transmission and regulation of cell apoptosis etc.Mitochondria are dually regulated by nuclear DNA and mitochondrial DNA,making mitochondria more sensitive to various exogenous and endogenous toxic substances.The destruction of mitochondrial structure and function by drugs can lead to cell necrosis or apoptosis.In recent years,studies have found that the mitochondria of various organ cells are one of the main targets of drug toxicity.Drugs can cause mitochondrial toxicity through a variety of ways.Mitochondrial damage is an important feature of many drug organ toxicity in the early stage.This paper mainly reviews common clinical drugs that induce mitochondrial toxicity in different organs and briefly discusses the mechanism of drug-mediated mitochondrial toxicity.In addition,we will also focus on the current commonly used mitochondrial toxicity evaluation models and evaluation techniques in order to provide ideas for the prevention and diagnosis of drug-mediated organ damage.

关 键 词：线粒体 线粒体毒性 器官毒性 临床药物 中药 评价模型 评价技术 高通量 

分 类 号：R285.5[医药卫生—中药学]