肝毒性评价体外替代模型研究进展
Research progress of in vitro alternative models for hepatotoxicity evaluation
万思雨 1赵晓晗 1肖筱璇 1宋佳 1杨杏芬1
作者信息
- 1. 南方医科大学食物安全与健康研究中心国家药监局化妆品安全评价重点实验室广东省热带病研究重点实验室,广州 510515
- 折叠
摘要
随着"3R原则"及"21世纪毒理学测试:远景与策略"的提出,毒理学评价的重点从体内测试转向了体外模型的应用,从而推动了体外替代模型的发展,毒性替代模型也受到越来越多学者的关注.肝脏是外源化学物质代谢的重要场所,一些经肝脏代谢的外源化学物会引起以炎症、氧化应激和坏死为特征的肝脏损害,因此,利用肝毒性替代模型来预测外源化学物的肝毒性至关重要.本文重点概述了 2D肝细胞、肝脏切片和3D肝脏肝毒性评价体外替代模型的现状和发展,同时对药物性肝损伤(drug-induced liver injury,DILI)生物标志物、DILI诊断方法以及与DILI相关的新兴技术进行了系统的阐述.
Abstract
With the introduction of the principles of the"3R"and the"Toxicology Testing in the 21st Century:Vision and Strategy",the focus of toxicological evaluation has shifted from in vivo testing to the application of in vitro models,thereby promoting the development of in vitro alternative models and attracting increasing attention from scholars.The liver is an important site for the metabolism of exogenous chemicals,and some exogenous chemicals metabolized by the liver can cause liver damage characterized by inflammation,oxidative stress,and necrosis.Therefore,it is crucial to use hepatotoxicity alternative models to detect the hepatotoxicity of exogenous chemicals.This article focused on the research of the in vitro alternative models of 2D hepatocytes,liver slices,and 3D liver for the evaluation of hepatotoxicity,and also provided a systematic description of the biomarkers of drug-induced liver injury(DILI),diagnostic methods for DILI,and emerging technologies related to DILI.
关键词
肝毒性/体外替代模型/生物标志物Key words
hepatotoxicity/in vitro alternative models/biomarkers引用本文复制引用
基金项目
国家重点研发计划(2022YFF0711100)
出版年
2024
NETL
NSTL
万方数据