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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 cardiac toxicity and its molecular mechanism of astemizole using zebrafish as experimental animal. Methods AB-line zebrafish (24 h post-fertilization) were exposed to different concentrations of astemizole. After 24 h of treatment, the mortality was measured and the morphology of the heart was observed under a microscope The changes of heart rate were recorded. The changes of cardiac function-related gene expression were detected by RT-q PCR. Results Seventeen heart-related genes (CAV1.3a, CAV1.3b, HCN2, HCN4, KCNH2a) were gradually decreased in the zebrafish embryo with the increase of astemizole concentration. , KCNQ1 and KCNE4) were down-regulated. Conclusions Astemizole has a dose-dependent effect on the cardiotoxicity of zebrafish embryos, and the mechanism of cardiotoxicity is likely to interfere with the expression of various ion channels related genes in the heart first and then interfere with the normal function of ion channels and finally trigger Cardiac toxicity.