体外三维肝细胞模型在药物肝毒性评价中的应用  

Application of three-dimensional models in prediction of drug-induced hepatotoxicity

作　　者：何原子 张雷 吴春勇[1,2] 张峻颖[4] HE Yuanzi;ZHANG Lei;WU Chunyong;ZHANG Junying(Key Laboratory of Drug Quality Control and Pharmacovigilance,Ministry of Education,China Pharmaceutical University,Nanjing 210009,China;Department of Pharmaceutical Analysis,China Pharmaceutical University,Nanjing 211198,China;Shandong Institute for Food and Drug Control,Jinan 250101,China;Department of Pharmaceutics of Traditional Chinese Medicine,China Pharmaceutical University,Nanjing 211198,China)

机构地区：[1]中国药科大学药物质量与安全预警教育部重点实验室,江苏南京210009 [2]中国药科大学药物分析教研室,江苏南京211198 [3]山东省食品药品检验研究院,山东济南250101 [4]中国药科大学中药制剂教研室,江苏南京211198

出　　处：《药学研究》2021年第10期678-683,共6页Journal of Pharmaceutical Research

基　　金：国家自然科学基金(No.82074128、81673681);江苏省市场监督管理局科技计划项目(No.KJ207558);国家药品监督管理局化学药品杂质谱研究重点实验室开放课题(No.NMPA-KLIPCD-2020-01)。

摘　　要：肝毒性是药物治疗过程中常见的副作用,也是导致新药临床试验失败以及药物撤市的主要原因。建立可以有效识别药物肝毒性的体外模型对于新药研发至关重要。传统的二维(2D)模型在培养过程中会逐渐丧失肝脏特异性功能,无法准确评价药物肝毒性。新兴的三维(3D)培养技术可模拟体内细胞微环境,有利于肝细胞的体外组装,从而使3D肝细胞模型表现出与体内肝细胞相似的表型以及药物毒性反应,在肝毒性评价方面具有很大潜力。Hepatotoxicity is a common side effect during drug treatment,and also the main reason for the failure of clinical trials and the withdrawal of drugs from the market.Therefore,it is crucial to develop an in vitro model that could effectively identify the drug hepatotoxicity for the new drug research and development.However,traditional hepatocyte models are limited due to the loss of the specific liver functions during two-dimensional(2 D)culture,thus failing to accurately evaluate the hepatotoxicity.The emerging three-dimensional(3 D)culture technology provides benefits for the in vitro assemble of hepatocytes by simulating the physiological microenvironment.Therefore,3 D hepatocytes could exhibit in vivo-like phenotypes and reactions to drug toxicity and have great potential in the evaluation of hepatotoxicity.

关 键 词：3D模型 肝毒性 3D细胞培养 药物筛选 

分 类 号：R917[医药卫生—药物分析学]