特异质型药物性肝损伤体内评价模型研究进展

doi:10.19803/j.1672-8629.20230802

摘要/Abstract

摘要： 目的总结特异质型药物性肝损伤（idiosyncratic drug-induced liver injury, IDILI）的评价研究进展,以期为IDILI评价和临床风险防控提供依据。方法从动物模型、数理模型、细胞模型等多方面论述IDILI模型的研究进展。结果与结论 目前关于IDILI机制研究取得了长足进展,并形成了线粒体损伤、免疫炎症、免疫稳态失衡、基因多态性等多种机制假说,并且针对部分假说建立了病证模型用于多种药物IDILI的评价研究。本课题组基于新发现“有毒”中药特异质肝损伤特点,提出了中药“病证毒理学”评价模式和方法,在此基础上证实了何首乌等中药的特异质肝损伤问题,并提出了中药特异质肝损伤免疫应激“三因致毒”机制假说,较好地阐释了中药IDILI发病特点和机制。

关键词: 特异质型, 药物性肝损伤, 机制假说, 中药, 病证毒理学, 病证模型, 线粒体损伤模型, 免疫炎症模型, 三因致毒

Abstract: Objective To summarize the research on the animal models of IDILI, then to provide a scientific basis for guiding IDILI research and establishing its clinical risk prevention and control measures. Methods The research progress of IDILI model was discussed from various aspects, such as animal model, mathematical model and cellular model. Results and ConclusionIn recent years, IDILI has been gradually confirmed by researchers, and formed some hypothesis, such as Mitochondrial dysfunction hypothesis, Inflammatory stress hypothesis, immunological stress-mediated tri-elements synergetic mechanism hypothesis and genetic polymorphism hypothesis. Based on the characteristics of newly discovered “toxic” Chinese medicine-related IDILI, this team put forward the evaluation model and method of “disease-syndrome-based toxicology” of traditional Chinese medicine, on the basis of which it confirmed the problem of IDILI of Polygoni Multiflori Radix and other traditional Chinese medicines, and put forward the hypothesis of “toxicity due to three causes” mechanism of the immune stress of IDILI of traditional Chinese medicines, which better explained the characteristics of the pathogenesis of traditional Chinese medicines and the mechanism of IDILI.

Key words: idiosyncratic, hepatotoxicity, mechanism hypothesis, traditional Chinese medicine, disease-syndrome-based toxicology, assessment model, mitochondrial dysfunction hypothesis, inflammatory stress hypothesis, toxicity due to three causes

中图分类号:

R994.11

高源, 石伟, 肖小河, 柏兆方, 王伽伯. 特异质型药物性肝损伤体内评价模型研究进展[J]. 中国药物警戒, 2024, 21(1): 33-39.

GAO Yuan, SHI Wei, XIAO Xiaohe, BAI Zhaofang, WANG Jiabo. Research progress on the animal models of idiosyncratic drug-induced liver injury[J]. Chinese Journal of Pharmacovigilance, 2024, 21(1): 33-39.

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