马兜铃酸肝脏致癌性争议及药物安全性思考  

Liver carcinogenicity caused by aristolochic acids:controversy and drug safety

作　　者：陈淑桢 董亚萍 文文[1,2] 王红阳 CHEN Shu-zhen;DONG Ya-ping;WEN Wen;WANG Hong-yang(National Center for Liver Cancer,Naval Medical University(Second Military Medical University),Shanghai 200438,China;International Cooperation Laboratory on Signal Transduction,Eastern Hepatobiliary Surgery Hospital,Naval Medical University(Second Military Medical University),Shanghai 200438,China;Cancer Institute,Fudan University Shanghai Cancer Center,Shanghai 200032,China)

机构地区：[1]海军军医大学(第二军医大学)国家肝癌科学中心,上海200438 [2]海军军医大学(第二军医大学)东方肝胆外科医院国际合作生物信号转导研究室,上海200438 [3]复旦大学附属肿瘤医院肿瘤研究所,上海200032

出　　处：《第二军医大学学报》2021年第1期1-7,共7页Academic Journal of Second Military Medical University

基　　金：国家科技重大专项重大新药创制专项(2018ZX09101002,2018ZX09101002-001-001)。

摘　　要：马兜铃酸是一类硝基菲类羧酸,广泛分布于马兜铃科植物中,主要化合物包括马兜铃酸Ⅰ、Ⅱ、Ⅲ、Ⅳ4种。长期服用含马兜铃酸药物可导致马兜铃酸肾病,诱发泌尿系统肿瘤。马兜铃酸的活性代谢产物可与DNA形成加合物,诱导基因发生A-T颠换突变,该突变常被作为马兜铃酸特征性标签。2017年Sci Transl Med报道指出,马兜铃酸及其衍生物与包括中国台湾在内的亚洲地区肝癌发生相关,认为应将避免使用马兜铃酸列为肝癌的一级预防策略。该报道引发了国内外研究者对于马兜铃酸是否具有肝脏致癌性的一系列探讨,本文即针对这一热点问题进行分析,主要讨论已有报道中马兜铃酸肝脏致癌性的争议点,科学客观地评价马兜铃酸与中国人群肝癌发生的关系,同时探讨含马兜铃酸药物安全使用仍需解决的问题,提出药物安全使用的一些思考。Aristolochic acids(AAs)is a group of nitrophenanthrene compounds comprised of AAⅠ,AAⅡ,AAⅢand AAⅣ,which are widely distributed in Aristolochiaceae plants.Long-term use of drugs containing AAs could lead to aristolochic acid nephropathy(AAN)and urinary tract tumors.Active metabolites of AAs could form AA-DNA adducts with DNA,which subsequently induce characteristic A-T transversion mutation known as AA mutational signature.In 2017,Sci Transl Med reported that AAs and their derivatives were widely implicated in liver cancers in Taiwan,China and throughout Asia,suggesting that additional measure should be taken for primary prevention through avoidance of AAs exposure.This report has triggered a series of worldwide discussion on whether AAs could cause liver cancer.We analyze this research focus in the present paper and mainly discuss the controversial points of the liver carcinogenicity related to AAs in the literature,so as to provide scientific and objective evidence to evaluate the association of AAs exposure with liver cancer development in Chinese population;meanwhile,the questions that need to be solved for the safety use of AAs are also presented,and some thoughts on them were put forward.

关 键 词：马兜铃酸 肾毒性 致癌性 肝肿瘤 用药安全 

分 类 号：R965.3[医药卫生—药理学] R735.7[医药卫生—药学]