阿司咪唑对斑马鱼心脏毒性的影响及其分子机制的研究  

Study on the effects of astemizole on cardiotoxicity of zebrafish and its molecular mechanism

作　　者：孙晨[1] 韩利文[1] 何秋霞[1] 张云[1] 王荣春[1] 王希敏[1] 韩建[1] 郭瑛楠 刘可春[1] SUN Chen HAN Liwen HE Qiuxia ZHANG Yun WANG Rongchun WANG Ximin HAN Jian GUO Yingnan LIU Kechun(Biology Institute of Shandong Academy of Sciences, Key Laboratory of Drug Screening Technology of Shandong Academy of Sciences, Key Laboratory for Biosensor of Shandong Province, Ji＇nan, Shandong 250103, China)

机构地区：[1]山东省科学院生物研究所山东省科学院药物筛选技术重点实验室山东省生物传感器重点实验室,山东济南250103

出　　处：《中国现代医生》2017年第24期41-45,F0003,共6页China Modern Doctor

基　　金：山东省三院联合基金(ZR2015YL009);山东省科学院青年基金(2015QN011)

摘　　要：目的以斑马鱼作为实验动物,研究阿司咪唑的心脏毒性及其分子机制。方法选择受精后24 h(24 hours post fertilization)的AB系斑马鱼作为实验动物,分别暴露于不同浓度的阿司咪唑培养液中,处理24 h后,统计其死亡率并在显微镜下观察心脏形态的改变,记录心率变化,利用RT-q PCR技术检测心脏功能相关基因表达的改变。结果随着阿司咪唑浓度的升高,斑马鱼胚胎逐渐出现死亡、心囊水肿、心脏畸形、心率下降等情况;7种心脏功能相关基因(CAV1.3a、CAV1.3b、HCN2、HCN4、KCNH2a、KCNQ1和KCNE4)的表达均有所下调。结论阿司咪唑对斑马鱼胚胎的心脏毒性具有一定的剂量依赖性,且该心脏毒性的作用机制很可能是首先干扰心脏中各离子通道相关基因的表达,进而干扰离子通道的正常功能,最终引发心脏毒性。Objective To study the cardiotoxicity of astemizole and its molecular mechanism by using zebrafish as the experimental animals. Methods Twenty-four post fertilization AB-zebrafish were selected as experimental animals and exposed to different concentrations of astemizole solution. After 24 h treatment, the mortality was calculated and the morphological changes of the heart were observed under the microscope. The heart rate changes were recorded. RT- qPCR technique was used to detect changes in cardiac function-related gene expression. Results As the concentration of astemizole was increased, zehrafish embryos gradually showed death, heart sac edema, heart deformity, heart rate decline and so on; the expression of seven cardiac function-related genes（CAV1.3a, CAV1.3h, HCN2, HCN4, KCNH2a, KCNQ1 and KCNE4） were down-regulated. Conclusion Astemizole has a dose-dependent effect on the cardiac toxicity of zebrafish embryos. The mechanism of cardiotoxicity is likely to first interfere with the expression of each ion channel-related genes in the heart, and then interfere with the normal function of the ion channel, ultimately leading to cardiotoxicity.

关 键 词：阿司咪唑 斑马鱼 心脏毒性 分子机制 

分 类 号：R965[医药卫生—药理学]