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斑马鱼模型在药物研发早期肾脏毒性中的应用研究

梁锦锋 朱勇 张洪瑶 劳乔聪 马敏康 李春启

中国比较医学杂志2016,Vol.26Issue(9):30-35,6.
中国比较医学杂志2016,Vol.26Issue(9):30-35,6.DOI:10.3969/j.issn.1671-7856.2016.09.006

斑马鱼模型在药物研发早期肾脏毒性中的应用研究

Study on the application of zebrafish model in the early stage of renal toxicity in drug development

梁锦锋 1朱勇 1张洪瑶 1劳乔聪 2马敏康 1李春启2

作者信息

  • 1. 浙江省药品化妆品审评中心,杭州 310012
  • 2. 杭州环特生物科技股份有限公司,杭州 310012
  • 折叠

摘要

Abstract

Objective To evaluate the renal toxicity of vancomycin hydrochloride and irbesartan tablets using the zebrafish model. Methods After construction of AB zebrafish kidney model, the fish were treated with drug after fertilization 2 days (2 dpf) to 5 dpf. At the end of the experiment, the number of renal edema zebrafish was counted in each experimental group to evaluate the renal toxicity of drugs. Results The zebrafish development was normal and no obvious toxicity at the dose of 16�4 ng/fish (1/10 MNLD) for vancomycin, and zebrafish renal edema occurred rate was 3�3%, 10% and 10% respectively at the dose of 54�7 ng/fish (1/3 MNLD), 164 ng/fish (MNLD) and 273 ng/fish ( LD10 ) with the death rate of 0%, 0% and 16�7%, respectively, which indicated that there was significant renal toxicity of vancomycin at the dose of 54�7 ng/fish (1/3MNLD) to 273 ng/fish (LD10). Irbesartan didn’t induce renal toxicity at the dose of 8�3 μg/mL (1/10 MNLC) to 91 μg/mL (LC10). Conclusions The zebrafish model of renal toxicity can be used for the early evaluation of drug renal toxicity and we made evaluation of the renal toxicity of vancomycin and irbesartan with this model.

关键词

斑马鱼/肾毒性/新药研发/万古霉素/厄贝沙坦

Key words

Zebrafish/Renal toxicity/New drug evaluation/Vancomycin/Irbesartan

分类

医药卫生

引用本文复制引用

梁锦锋,朱勇,张洪瑶,劳乔聪,马敏康,李春启..斑马鱼模型在药物研发早期肾脏毒性中的应用研究[J].中国比较医学杂志,2016,26(9):30-35,6.

基金项目

浙江省食品药品监管系统科技计划项目(2014002)。 ()

中国比较医学杂志

OA北大核心CSTPCD

1671-7856

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