基于斑马鱼模型的中药致肝脏毒性评价的研究进展  

Research progress on evaluation of hepatotoxicity of traditional Chinese medicine based on zebrafish model

作　　者：原杨 尚悦 王鹏 樊慧蓉[2] 侯文彬 YUAN Yang;SHANG Yue;WANG Peng;FAN Huirong;HOU Wenbin(Tianjin University of Traditional Chinese Medicine,Tianjin 301617,China;Institute of Radiology Medicine Chinese Academy of Medical Sciences,Tianjin 300192,China;Tianjin Hankang Medical Biotechnology Co.,Ltd.,Tianjin 300409,China)

机构地区：[1]天津中医药大学,天津301617 [2]中国医学科学院放射医学研究所,天津300192 [3]天津市汉康医药生物技术有限公司,天津300409

出　　处：《药物评价研究》2024年第5期933-940,共8页Drug Evaluation Research

基　　金：内蒙古自治区科技重大专项(2019ZD004);内蒙古自治区科技计划(2020GG0199)。

摘　　要：中药的广泛使用,提高了肝脏毒性发生风险。斑马鱼模型在肝脏毒性研究中显现出较大潜力的同时,也面临评价标准难以统一的问题。在使用斑马鱼进行药物肝损伤检测和评价之前应先明确其在不同生长阶段的肝功能状态,利用斑马鱼胚胎和幼鱼的通体透明的特点,以胚胎的孵化率、死亡率、畸形率作出初步的发育毒性判断,以幼鱼肝脏灰度值,肝脏面积大小,卵黄囊吸收程度作为药物是否具有肝脏毒性的判断标准,利用成鱼肝脏容易分离的特点研究肝脏毒性的作用机制。检测时可根据这些指标判断斑马鱼肝脏发育阶段,为其是否发生药物肝损伤提供依据,从而进一步提高临床用药安全性。综述了不同发育时期斑马鱼评估中药肝毒性的研究方法及研究进展,以期为后续中药的肝脏毒性评价提供参考。The extensive use of Chinese medicine increases the risk of liver toxicity.While zebrafish model shows great potential in hepatotoxicity research,it also faces the problem that evaluation criteria are difficult to unify.Before using zebrafish for drug liver injury detection,the liver function status of zebrafish at different growth stages should be clearly defined.Given that the whole transparent characteristics of zebrafish embryos and juvenile fish,the preliminary developmental toxicity judgment can be made based on the hatching rate,mortality rate and deformity rate of embryos.The degree of yolk sac absorption is used as the criterion to judge whether the drug has hepatotoxicity.The mechanism of hepatotoxicity is studied by using the characteristics of easy separation of adult fish liver.These indicators can be used to determine the liver development stage of zebrafish and provide evidence for whether drug liver injury occurs,so as to further improve clinical drug safety.This paper reviewed the research methods and progress of evaluating hepatotoxicity of traditional Chinese medicine in zebrafish at different developmental stages,in order to provide reference for the subsequent detection of hepatotoxicity of traditional Chinese medicine.

关 键 词：中药 斑马鱼 肝损伤 肝毒性 药物性肝损伤 肝脏毒性检测 

分 类 号：R965.3[医药卫生—药理学] R969.4[医药卫生—药学]