中药影响hERG钾通道致长-QT综合征机制的研究进展  

Advances in research on the mechanism of long-QT syndrome caused by traditional Chinese medicine affecting hERG potassium channel

作　　者：张钰浩 颜才川 王芳 李宝馨[1] 杨宝峰[1] ZHANG Yu-hao;YAN Cai-chuan;WANG Fang;LI Bao-xin;YANG Bao-feng(School of Pharmacy,Harbin Medical University,Harbin 150081,China)

机构地区：[1]哈尔滨医科大学药学院

出　　处：《药学学报》2019年第11期1881-1887,I0003,共8页Acta Pharmaceutica Sinica

基　　金：国家自然科学基金资助项目(81673636)

摘　　要：药物诱发心脏毒性是近年来备受关注的问题,心脏毒性是药物由市场撤回的主要原因,而长-QT综合征是心脏毒性的重要表现之一,hERG钾通道是药物诱发心律失常和抗心律失常药物作用的重要靶点。中药是我国传统医药,临床使用历史悠久且范围广泛,但中药致多器官毒性仍是有待解决的难题,一些已投入临床使用的中药制剂因潜在的心脏毒性或引起严重的心律失常而被迫从市场撤回。据报道,有50余种临床常用中药产生致心律失常的心脏毒性,其中20余种是通过作用于hERG钾通道致心律失常。因此,寻找药物诱发的长-QT综合征机制及药物干预的调控靶点是当今医药领域的重点研究目标。本文总结了以Ikr/hERG钾通道为主要作用靶点的相关中药诱发长-QT综合征的机制,为临床上合理使用相关中药、避免心脏毒性以及研发药物干预的调控靶点提供理论依据。Drug-induced cardiotoxicity is recently a major concern.Cardiotoxicity is the leading cause of drug withdrawal from the market.Long-QT syndrome is one of the most important manifestations of cardiotoxicity.hERG potassium channel is an important target of drug-induced arrhythmia and antiarrhythmia drugs.Traditional Chinese medicine is a traditional medicine in China with a long history and a wide range of clinical use.However,the multi-organ toxicity caused by traditional Chinese medicine is still a problem to be solved.Some traditional Chinese medicines already in clinical use have been withdrawn from the market because of their potential cardiotoxicity or severe arrhythmias.The cardiac toxicity of more than 50 kinds of traditional Chinese medicines causing arrhythmia was reported,while more than 20 of them are induced by affecting on the hERG potassium channels.Therefore,finding out the mechanism of drug-induced long-QT syndrome and the regulatory target of drug intervention is the key research goal in today’s medical field.In this paper,we summarized the mechanisms of long-QT syndrome induced by traditional Chinese medicine with Ikr/hERG potassium channel as the main target.It provides a theoretical basis for the rational use of related traditional Chinese medicine in clinical practice,the avoidance of cardiac toxicity and the development of regulatory targets for drug intervention.

关 键 词：中药 心脏毒性 长-QT综合征 HERG 

分 类 号：R965[医药卫生—药理学]