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王雪,刘可春,王荣春,王希敏,韩利文,孙晨,张云,何秋霞,侯海荣.2015.马兜铃酸对斑马鱼胚胎肾毒性作用.动物学杂志,50(5):773-779.
马兜铃酸对斑马鱼胚胎肾毒性作用
Nephrotoxic Effects of Aristolochic Acid in Zebrafish (Danio rerio) Embryos
投稿时间:2014-12-11  修订日期:2015-06-25
DOI:DOI: 10.13859/j.cjz.201505014
中文关键词:  斑马鱼  肾脏毒性  马兜铃酸。
英文关键词:Zebrafish  Nephrotoxicity  Aristolochic acid.
基金项目:
作者单位E-mail
王雪 山东省科学院生物研究所 wangxue197811@yahoo.com.cn 
刘可春 山东省科学院生物研究所 hliukch@sdas.org 
王荣春 山东省科学院生物研究所  
王希敏 山东省科学院生物研究所  
韩利文 山东省科学院生物研究所  
孙晨 山东省科学院生物研究所  
张云 山东省科学院生物研究所  
何秋霞 山东省科学院生物研究所  
侯海荣 山东省科学院生物研究所  
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中文摘要:
      目的:利用斑马鱼胚胎研究马兜铃酸的肾脏毒性作用。方法:选用肾脏发育完成(受精后3天)的斑马鱼胚胎,用马兜铃酸进行染毒处理,通过观察胚胎的表型变化及死亡情况,分析马兜铃酸对胚胎的毒性作用及规律;利用肾脏荧光观察及肾脏组织切片,观察马兜铃酸处理后胚胎肾脏形态和肾脏组织结构的改变情况;利用qPCR检测马兜铃酸处理前后nephrin的表达变化,初步探讨足细胞在马兜铃酸毒性作用中的功能状态。结果: 20 μmol/L马兜铃酸处理24 h后,胚胎出现明显眼周水肿表现,在高浓度组(40~80μmol/L),除眼周水肿外,胚胎血循环系统功能出现异常,表现为心率降低、血流缓慢及甚至停滞;镜下观察发现,马兜铃酸处理组胚胎肾脏出现肾小球囊性膨胀、前肾管囊性扩张和形态异常改变;切片结果显示马兜铃酸处理组胚胎肾脏组织结构受到损害,表现为肾小球结构疏松、囊性扩张,前肾管上皮细胞细胞排列松散、紊乱及管腔扩张样改变;qPCR结果显示马兜铃酸处理组斑马鱼胚胎nephrin的表达水平比对照组显著降低(P﹤0.01)。结论:马兜铃酸能损害斑马鱼胚胎肾脏结构和功能,其毒性作用与肾小球足细胞的功能改变有关。
英文摘要:
      Objective: To study the nephrotoxicity of aristolochic acid in a zebrafish embryo model. Methods: Zebrafish embryos at 3 days post-fertilization stage were treated with aristolochic acid. Morphological changes of embryos and kidney were observed. Histological structure of kidney were further examined by tissue sections. The expression level of Nephrin was tested by qPCR to explore the podocyte function in embryo kidney treated with aristolochic acid. Results: Embryos treated with 20 μmol/L AA for 24h exhibited periocular edema and malformed kidney phenotypes. As the exposure dosages of AA increased, besides periocular edema, embryos also displayed impaired blood circulation, such as decreased heart rate and blood flow, and even blood stasis.Embryos treated with AA displayed cystic glomeruli and disorganized pronephric tubules. qPCR showed that AA treatment can significantly down-regulate the expression of nephrin in comparison with mock-control littermates(P<0.01). Conclusion: AA caused profound nephrotoxicity in histological structure and biological function of zebrafish embryos. Dysfunction of podocyte may involve in AA-induced renal impairment.
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