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肝毒性风险的体外早期发现和预测
引用本文:刘文静,武之涛,潘国宇.肝毒性风险的体外早期发现和预测[J].金属学报,2021,26(8):923-930.
作者姓名:刘文静  武之涛  潘国宇
作者单位:1.南京中医药大学,南京 210000,江苏;;2.中国科学院上海药物研究所安全评价研究中心,上海 201203
基金项目:国家自然科学基金(81872927)
摘    要:药物诱导的肝损伤(DILI)是临床研究中药品研发失败和药品上市后撤回的主要原因。动物模型对药物诱导的肝损伤风险进行预测,因为物种差异,准确性较差。因此,有效、快速的人源性体外肝毒性预测模型一直受到学术界和工业界的重视。本文综述了常用的体外肝毒性预测模型,以及对肝细胞培养方法的改进,尤其是共培养体系和三维培养系统可以有效提高体外肝毒性预测模型的准确性,也为临床药物肝毒性机制研究提供参考。

关 键 词:肝毒性  药物诱导的肝损伤  体外肝脏替代模型  
收稿时间:2021-06-23
修稿时间:2021-07-13

Early dectection and prediction hepatotoxic risk in vitro
LIU Wenjing,WU Zhitao,PAN Guoyu.Early dectection and prediction hepatotoxic risk in vitro[J].Acta Metallurgica Sinica,2021,26(8):923-930.
Authors:LIU Wenjing  WU Zhitao  PAN Guoyu
Affiliation:1.Nanjing University of Chinese Medicine, Nanjing 210000, Jiangsu, China;2.Center for Drug Safety Evaluation and Research (CDSER), Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China
Abstract:Drug-induced liver injury (DILI) is a major cause of drug failure in clinical trial and market withdrawal. Animal models are utilized to predict the risk of drug-induced liver injury. However, due to species differences, the accuracy of animal models is poor. Multiple human-derived hepatotoxic prediction models have been developed to assess this potential risk. This article reviews commonly used in vitro hepatotoxic models, as well as the latest improvement of hepatocyte culture protocols, especially hepatic co-culture system and 3D culture system in order to improve the accuracy of hepatotoxic risk prediction, which may also guide the liver toxicity mechanistic investigation in clinic.
Keywords:hepatotoxicity  drug-induced liver injury  alternative models of liver  
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