异烟肼致线粒体损伤引起药物性肝损伤研究进展  

Mitochondria dysfunction is involved in the pathogenesis of isoniazidinduced hepatotoxicity

作　　者：郭瑶雪[1,2,3] 邓晔[1,2,3] 李春[1,2,3] 贺蕾艳 彭文兴[1,2] 

机构地区：[1]中南大学湘雅二医院药剂科 [2]中南大学临床药学研究所 [3]中南大学药学院

出　　处：《中国临床药理学与治疗学》2015年第3期356-360,共5页Chinese Journal of Clinical Pharmacology and Therapeutics

摘　　要：近年国内外研究表明,线粒体功能异常是各种肝损伤(肝功能衰竭、肝硬化、脂肪肝等)发生的重要机制之一,而在药物性肝损伤发展过程中线粒体也起着重要作用。异烟肼是临床应用广泛、效果显著的抗结核药,但在治疗过程中常引起药物性肝损伤。在某种程度上妨碍了结核病的治疗。研究发现线粒体损伤是异烟肼肝损伤发生发展中关键一环,异烟肼及其毒性产物肼可通过激动氧化应激反应;抑制线粒体呼吸链中酶的活性;干扰细胞能量代谢及对线粒体膜产生攻击等方式使其功能异常,最终导致线粒体损伤,进而启动细胞凋亡程序。本文将对线粒体在异烟肼致药物性肝损伤中的作用进行综述,旨在从亚细胞水平解释异烟肼致肝毒性的机制,为阐明异烟肼的肝毒性提供更为有力的证据。Emerging evidence shows mitochondria dysfunction is one of the mechanisms of various liver injury,such as liver failure,cirrhosis and adipose infiltration,especially drug induced liver injury（DILI）.Isoniazid is widely used in anti-tuberculosis（anti-TB）treatment but well known for the apparent liver injury which sometimes limit the efficacy of anti-TB regimen.There is growing evidence that mitochondria dysfunction is critial in INH-induced DILI.INH and its toxic metabolites induced oxidant stress of mitochondria,inhibition of respiratory chain enzymes and impairment of energy homeostasis,disruption of mitochondria membrane,finally led to mitochondria dysfunction and triggered apoptosis.This review discusses this emerging new paradigms of INH-induced DILI and highlights recent insights of sub-cell level in the mechanisms,as well as points to the existing large gaps in our understanding of the pathogenesis.

关 键 词：异烟肼 药物性肝损伤 线粒体功能异常 

分 类 号：R969[医药卫生—药理学]