异烟肼引起的肝毒性及其影响因素的研究进展  

An updated review on isoniazid-induced hepatotoxicity and it’s influencing factors

作　　者：徐泽月 郭宏丽 胡雅慧 陈峰 许静[1] 田曼[1] XU Ze-yue;GUO Hong-li;HU Ya-hui;CHEN Feng;XU Jing;TIAN Man(Department of Pharmacy,Children's Hospital of Nanjing Medical University,Nanjing 210008,China;School of Basic Medicine and Clinical Pharmacy,China Pharmaceutical University,Nanjing 211198,China)

机构地区：[1]南京医科大学附属儿童医院药学部,南京210008 [2]中国药科大学基础医学与临床药学学院,南京211198

出　　处：《中国新药杂志》2022年第22期2251-2256,共6页Chinese Journal of New Drugs

基　　金：江苏省卫生健康委员会特聘医学专家项目(2019)。

摘　　要：结核病是一种由结核分枝杆菌造成的细菌传染病,异烟肼在防治结核病的过程中发挥了重要作用。然而,异烟肼引起的肝毒性给患者带来了额外的健康风险。异烟肼及其代谢产物是引起肝毒性的重要物质基础,本文主要通过对异烟肼体内代谢转化过程中关键药物代谢酶N-乙酰基转移酶2(NAT2)、细胞色素酶P4502E1(CYP2E1)、谷胱甘肽巯基转移酶(GST)相关的基因多态性分析,同时结合年龄因素讨论关键酶个体发育对异烟肼代谢转化的影响,从异烟肼代谢转化的角度剖析异烟肼引起肝毒性的内在机制。Tuberculosis is a bacterial infectious disease caused by Mycobacterium tuberculosis and isoniazid plays an important role in the prevention and treatment of this disease. However, the hepatotoxicity caused by isoniazid(INH) is still a major clinical problem. INH and its metabolites are believed to be involved in cytotoxicity. This article focuses on the association between hepatotoxicity and genetic polymorphisms, and ontogeny of the key drug-metabolizing enzymes, including NAT2, CYP2 E1 and GST, which are responsible for the metabolic transformation of isoniazid. Age is also extensively discussed as a key factor influencing the expression and activity of these metabolizing enzymes. This review article aims to summarize the potential mechanisms of INH-induced hepatotoxicity from the perspective of metabolic transformation of isoniazid. This paper therefore helps us to better understand the current mechanistic findings for INH-induced liver injury.

关 键 词：异烟肼 肝毒性 药物性肝损伤 药物代谢酶 个体发育 基因多态性 

分 类 号：R966[医药卫生—药理学]