观察时间和换液频率对斑马鱼评价模型的影响  

Effects of observation time and administration frequency on zebrafish evaluation model

作　　者：高绪聪[1,2] 孙程颖 韩利文 韩建[3] 申秀萍[1,2] GAO Xu-cong;SUN Cheng-ying;HAN Li-wen;HAN Jian;SHEN Xiu-ping(Tianjin Institute of Pharmaceutical Research New Drug Evaluation Co.Ltd,GLP Lab,Tianjin 300301,China;Tianjin Engineering Research Center of Drug Preclinical Assessment Technology,GLP Lab,Tianjin 300301,China;Shandong Province Biology Institute of Shandong Academy of Sciences,Key Lab for Drug Screening Technology,Ji＇nan 250014,China)

机构地区：[1]天津药物研究院新药评价有限公司GLP实验室,天津300301 [2]天津市新药非临床评价技术工程中心GLP实验室,天津300301 [3]山东省科学院生物研究所药物筛选技术重点实验室,山东济南250014

出　　处：《中国药理学通报》2018年第12期1774-1776,共3页Chinese Pharmacological Bulletin

基　　金：国家科技部“重大新药创制”科技重大专项(No2015ZX09501004); 天津市科技计划项目(No16PTGCCX00090)

摘　　要：目的通过设置不同的观察时间和换液频率,研究两者对斑马鱼模型的影响,优化评价模型。方法分别进行斑马鱼胚胎给药5 d,每天换液、实验7 d,每天换液及给药5 d不换液实验,检测3种实验方法中各组斑马鱼的死亡率、自由活动、形态发育和骨骼发育情况,并对3种实验方法的结果进行比较。结果较给药5 d每天换液实验,延长观察时间,使斑马鱼死亡率升高、畸形程度增加、骨骼矿化呈现出一定的剂量趋势,适当延长观察时间,可使药物的毒性作用表达更加充分;不换液实验中,斑马鱼死亡率略低、畸形程度减轻,不换液给药一定程度上降低了药物的毒性作用。结论定期更换药液,保证暴露浓度和适当延长观察时间,可使斑马鱼药物毒性评价模型的结果更加准确、可靠。Aim To study the effects of different observation time and liquid exchange frequency on zebrafish model and optimize the evaluation model. Methods De-membrane zebrafish embryos of 6 h fertilization were exposed for 5 days and changed solution for 4/5 every 24 hours. The mortality rate was measured during the experiment, and the autonomous activity, morphological development and bone development of young fish were detected at the end of the experiment. Meanwhile, the experiment was carried out for 7 days too, that was, after 5 days of exposure, the observation time was prolonged until the 7th day. No liquid exchange test was no change of solution during 5 days of exposure. The other test methods were the same, and the results of the three test methods were compared. Results Compared with the daily liquid exchange test for 5 days, prolonged observation time increased the mortality and the degree of deformity, showing a certain dose-effect of bone mineralization, and decreased the teratogenic dose of the positive drug all- trans retinoic acid （ATRA）. Proper prolongation of observation time could make the expression of drug toxicity more fully. In the non-exchange test, the mortality of zebrafish was slightly lower, the degree of deformity was reduced, and the teratogenic dose of the positive drug ATRA increased. The toxicity of the drug was reduced to a certain extent. Conclusion The results of drug toxicity evaluation model of zebrafish can be more accurate and reliable if the exposure concentration of drug is maintained by regular change of liquid and proper prolongation of observation time.

关 键 词：观察时间 换液频率 斑马鱼 毒性评价 形态发育 评分 骨骼发育 

分 类 号：R-332[医药卫生] R336