中药及天然药物对甲氨蝶呤致肝损伤保护作用的研究进展  

Research progress on protective effect of traditional Chinese medicine and natural medicine on methotrexate-induced liver toxicity

作　　者：朱露林 张奇 刘梦琴 刘沙 刘玉玲 秦路平 张巧艳 ZHU Lu-lin;ZHANG Qi;LIU Meng-qin;LIU Sha;LIU Yu-ling;QIN Lu-ping;ZHANG Qiao-yan(College of Pharmaceutical Sciences,Zhejiang Chinese Medical University,Hangzhou 310053,China;School of Pharmacy,Fujian University of Traditional Chinese Medicine,Fuzhou 350122,China)

机构地区：[1]浙江中医药大学药学院,浙江杭州310053 [2]福建中医药大学药学院,福建福州350122

出　　处：《中国中药杂志》2021年第7期1727-1737,共11页China Journal of Chinese Materia Medica

基　　金：国家自然科学基金项目(81973534)。

摘　　要：甲氨蝶呤(methotrexate, MTX)是临床常用的抗代谢药,可应用于多种疾病的治疗,但在治疗中出现的肝毒性严重限制了其临床使用。因此,如何防治MTX的肝毒性成了亟待解决的临床问题,基于此,该文就近年来关于中药和天然药物防治MTX致肝损伤的相关文献进行归纳分析,发现(1) MTX致肝损伤机制有叶酸途径、氧化应激损伤和腺苷途径,其中氧化应激学说是主要研究方向;(2)白芍等14种中药和天然药物提取物及小檗碱等21种天然单体化合物通过对抗氧化应激、抑制炎症反应、调控信号通路发挥抗MTX致肝损伤作用;(3)目前中药和天然药物防治MTX致肝损伤的研究中,存在机制研究片面、粗浅,与临床实践结合不够,实验设计欠规范,及缺乏新技术新方法的应用等不足。该文对中药及天然药物抗MTX致肝损伤的作用及机制进行系统综述,明确其研究现状和不足,以期提出新的研究策略和方向,为MTX的临床合理用药及抗MTX肝损伤的新药开发提供科学的依据。Methotrexate(MTX) is a commonly used antimetabolite, which can be used in the treatment of a variety of diseases. However, hepatotoxicity in the use of MTX severely limits its clinical use. Therefore, how to prevent and treat hepatotoxicity of MTX has become an urgent clinical problem. This paper summarizes and analyzes relevant literatures on the prevention and treatment of hepa-totoxicity caused by MTX with traditional Chinese medicines and natural medicines in recent years. MTX-induced hepatotoxicity mechanisms include folate pathway, oxidative stress damage and adenosine pathway, of which oxidative stress theory is the main research direction. A total of 14 kinds of traditional Chinese medicine and natural medicine extracts including white peony root, and 21 kinds of natural monomer compounds, including berberine, play an anti-MTX-induced hepatotoxic effect by resisting oxidative stress, inhibiting inflammation and regulating signal pathways. According to current studies on the prevention and treatment of hepatotoxicity induced by MTX with traditional Chinese medicines and natural medicines, there are insufficiencies, such as partial and superficial mechanism studies, inadequate combination of experimental research and clinical practice, non-standard experimental design and lack of application of advanced technologies and methods. This paper systematically reviewed the effects and mechanisms of traditional Chinese medicines and natural medicines against hepatotoxicity induced by MTX and defined current studies and deficiencies, in the expectation of proposing new study strategies and directions and providing scientific basis for rational clinical use of MTX and development of new drugs against MTX hepatotoxicity.

关 键 词：中药 天然药物 甲氨蝶呤 肝损伤 综述 

分 类 号：R285[医药卫生—中药学]