论含马兜铃酸中药的风险评估、安全用药与科学监管——马兜铃酸种类不同毒性各异,检控马兜铃酸Ⅰ/Ⅱ是关键  

Risk assessment, safe medication and scientific supervision of traditional Chinese medicine containing aristolochic acids——toxicity is different among aristolochic acids, and detection and control of aristolochic acid Ⅰ/Ⅱ is critical

作　　者：田婧卓 刘素彦 高月 张伯礼[3] 梁爱华[1] TIAN Jing-zhuo;LIU Su-yan;GAO Yue;ZHANG Bo-li;LIANG Ai-hua(Institute of Chinese Materia Medica,China Academy of Chinese Medical Sciences,Bejing 100700,China;Institute of Radiation Medicine Sciences,Academy of Miliary Medical Sciences,Academy of Miliary Sciences Bejing 100850,China;Tianjin University of Traditional Chinese Medicine,Tianjin 301617,China)

机构地区：[1]中国中医科学院中药研究所,北京100700 [2]军事科学院军事医学研究院辐射医学研究所,北京100850 [3]天津中医药大学,天津301617

出　　处：《中国中药杂志》2022年第14期3693-3700,共8页China Journal of Chinese Materia Medica

基　　金：国家自然科学基金项目(82192913,82174073,82104519);中国中医科学院(CACMS)创新工程项目(CI2021B016,CI2021A04801,CI2021A04803);中国中医科学院自选项目(ZZ-13-035-10,ZZ12-001,ZXKT21018,ZXKT20022)。

摘　　要：含马兜铃酸中药的安全性备受国内外关注,是临床使用和药品监管面临的重大难题。马兜铃酸类化合物(aristolo-chic acid analogues, AAAs)种类繁多,已报道的约有178种,按结构类型主要分为马兜铃酸类(aristolochic acids, AAs)和马兜铃内酰胺类(aristololactams, ALs)。AAAs种类不同,毒性差异很大:AA-Ⅰ的肾脏毒性和致癌性较强,AA-Ⅱ毒性低于AA-Ⅰ,而AA-Ⅳa、AA-Ⅰa无明显毒性。马兜铃科不同品种所含的AAAs种类和含量差异很大,有的品种如细辛、天仙藤所含的主要为无明显毒性的AAAs(如AA-Ⅳa)。复方制剂中AAAs含量与药味占比以及制备工艺等有关,有的制剂中AA-Ⅰ含量很低或测不出。因此笔者提出“AAAs种类不同,毒性各异,并非所有AAAs都有肾毒性和致癌性。含AAAs中药的毒性不应一概而论,检控AA-Ⅰ和AA-Ⅱ是关键”的学术观点。该文提出对含AAAs中药,不应因噎废食,应加强中药AAAs种类与含量的调研分析以及毒理学研究,制定AA-Ⅰ和AA-Ⅱ的限量标准,合理用药以及科学监管的建议。The safety problem of traditional Chinese medicine containing aristolochic acid is of great concern in China and abraod, which poses a challenge in clinical application and supervision. There are many types of aristolochic acid analogues(AAAs) and 178 have been reported. According to the structure, they are classified into aristolochic acids(AAs) and aristololactams(ALs). The toxi-city is remarkably different among AAAs of different types. For example, AA-Ⅰ has strong nephrotoxicity and carcinogenicity, and the toxicity of AA-Ⅱ is lower than that of AA-Ⅰ. Besides, AA-Ⅳa and AA-Ⅰa are considered to have no obvious nephrotoxicity and carcinogenicity. The types and content of AAAs are significantly different among traditional Chinese medicines derived from different Aristolochiaceae species. For example, Asari Radix et Rhizoma and Aristolochiae Herba mainly consist of AAAs without obvious toxicity(such as AA-Ⅳa). The content of AAAs in compound preparations is related to the proportions of the medicinals and the processing method. The content of AA-Ⅰ in some compound preparations is very low or below the detection limit. Therefore, the author concludes that AAAs of different types have different toxicity, but not all AAAs has nephrotoxicity and carcinogenicity. Moreover, the toxicity of traditional Chinese medicines containing AAAs should not be generalized and AA-Ⅰ and AA-Ⅱ should be emphasized. In this paper, it is suggested that traditional Chinese medicine containing AAAs should be used rationally and research, analysis, and toxicological study of AAAs species and content should be strengthened. In addition, limit standards of AA-Ⅰ and AA-Ⅱ should be formulated and science-based supervision should be performed.

关 键 词：马兜铃酸类 肾毒性 致癌性 限量标准 监管建议 

分 类 号：R288[医药卫生—中药学]