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[摘要]
目的 研究对乙酰氨基酚(APAP)对斑马鱼幼鱼的肝脏毒性,并验证斑马鱼模型用于药物肝毒性快速评价的实用性。方法 以发育72 hpf的肝脏荧光转基因斑马鱼幼鱼(L-FABP:EGFP)为实验对象,不同浓度的APAP分别处理斑马鱼幼鱼,于处理后24、48、72 h,体视显微镜下观察幼鱼的死亡率、肝脏形态学变化和卵黄囊吸收情况,荧光显微镜下观察APAP对幼鱼肝脏荧光的影响。结果 APAP对斑马鱼幼鱼存活率的影响呈剂量和时间相关性。APAP处理后的幼鱼肝脏形态出现异常、肝脏颜色变暗,卵黄囊肿。与空白对照组相比,APAP处理后的幼鱼肝组织L-FABP荧光表达明显下降,肝脏明显萎缩退化。结论 APAP对斑马鱼幼鱼具有肝脏毒性。肝脏荧光转基因斑马鱼模型快速评价药物的肝脏毒性具有较好的应用前景。
[Key word]
[Abstract]
Objective To determine the hepatotoxicity of acetaminophen (APAP) in larval zebrafish and to validate the practicability of zebrafish model for rapid assessment of drug hepatotoxicity. Methods 72 hpf liver fluorescence transgenic zebrafish larvae (L-FABP: EGFP) were administered with APAP at four dosage series for 24, 48, and 72 h, respectively. Larval zebrafish mortality, liver morphology, yolk sac retention, and changes in liver fluorescence were evaluated to study the hepatotoxic effects of APAP. Results The effect of APAP on mortality of larval zebrafish was dose- and time-dependent. Larval zebrafish treated with APAP exhibited liver malformation, discoloration, hepatatrophia, and vitelline cyst. Compared with the control group, the liver fluorescence intensity significantly decreased in the larval zebrafish treated with APAP. Conclusion APAP could induce the liver damage in larval zebrafish. And using zebrafish as a reliable mammal model for screening hepatotoxic agents has good application prospects.
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[基金项目]
国家自然科学基金(81202584),山东省科学院青年科学基金项目(鲁科院字2012第100号)资助