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张凯玉,王圆,胡燕燕,张静,施雯婷,赵外荣,唐靖一,周忠焱.斑马鱼缓慢性心律失常模型的构建[J].中国实验动物学报,2022,30(3):358~369.
斑马鱼缓慢性心律失常模型的构建
Establishment of a bradycardiac arrhythmia model in zebrafish
投稿时间:2022-01-11  
DOI:10. 3969 / j.issn.1005-4847. 2022. 03. 008
中文关键词:  缓慢性心律失常  斑马鱼  维拉帕米  心脏毒性  抗心律失常药物
英文关键词:bradycardiac arrhythmia  zebrafish  verapamil  cardiotoxicity  antiarrhythmic drugs
基金项目:
作者单位E-mail
张凯玉 上海中医药大学附属龙华医院心血管研究室,上海 200032 690664521@ qq. com 
王圆 上海中医药大学附属龙华医院心血管研究室,上海 200032  
胡燕燕 上海中医药大学附属龙华医院心血管研究室,上海 200032  
张静 上海中医药大学附属龙华医院心血管研究室,上海 200032  
施雯婷 上海中医药大学附属龙华医院心血管研究室,上海 200032  
赵外荣 1. 上海中医药大学附属龙华医院心血管研究室,上海 200032
2. 上海中医药大学附属龙华医院中西医结合心脏康复中心,上海 200032 
 
唐靖一 1. 上海中医药大学附属龙华医院心血管研究室,上海 200032
2. 上海中医药大学附属龙华医院中西医结合心脏康复中心,上海 200032
3. 上海中医药大学产业发展中心,上海 200032 
dr_tang@ 163. com 
周忠焱 上海中医药大学附属龙华医院心血管研究室,上海 200032 biozzy@ 126. com 
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中文摘要:
       目的 建立一种简单易行、重复性好的斑马鱼缓慢性心律失常模型及其评价体系。 方法 选用 24 hpf 的野生型和心脏标记绿色荧光蛋白的转基因斑马鱼,分别用不同浓度的维拉帕米、普罗帕酮、美托洛尔、胺碘酮、美西律干预 48 h,检测斑马鱼生存率、心率、心博量、心输出量、射血分数、心室舒张期和收缩期面积差值、静脉窦与动脉球(SV-BA)间距等心脏功能和心脏毒性评价指标。 结果 药物毒性的评价中,半数致死浓度( IC50)排序为普罗帕酮 < 美西律 < 胺碘酮 < 美托洛尔和维拉帕米。 维拉帕米显著降低斑马鱼心率、心输出量、射血分数及心室舒张期和收缩期面积差值,增加 SV-BA 间距;普罗帕酮降低斑马鱼心率及心输出量;美托洛尔降低斑马鱼心率; 胺碘酮降低斑马鱼心率,增加 SV-BA 间距;美西律增加 SV-BA 间距。 结论 维拉帕米、普罗帕酮、美托洛尔、胺碘酮均可制备斑马鱼缓慢性心律失常模型,其中维拉帕米效果最佳。本研究提出运用维拉帕米等抗心律失常药物构建缓慢性心律失常斑马鱼模型,并建立了相应的评价指标,对缓慢性心律失常的研究及药物研发均具有重要的意义。
英文摘要:
       Objective To establish a simple and reproducible model and its evaluation system for bradycardiac arrhythmia in Zebrafish. Methods Wild-type and heart-labeled GFP transgenic zebrafish were employed in this study after 24 h of fertilization. Twenty-four hpf (hour post-fertilization) zebrafish embryos were treated with various concentrations of verapamil, propafenone, metoprolol, amiodarone, and mexiletine for 48 hours, then the cardiac function and cardiotoxicity, including survival rate, heart rate, stroke volume, cardiac output, ejection fraction, area difference between ventricular diastole and systole and the distance between sinus venosus and bulbus arteriosus (SV-BA), were observed in each group. Results To evaluate drug toxicity, the median lethal concentration ( IC50 ) was ranked as propafenone < mexiletine < amiodarone < metoprolol and verapamil. After treatment with verapamil, the heart rate, cardiac output, ejection fraction and difference between ventricular diastolic and systolic areas significantly decreased in Zebrafish, while the distance of SV-BA increased. Treatment of propafenone reduced the heart rate and cardiac output in Zebrafish. Treatment of metoprolol decreased the heart rate in Zebrafish. Treatment of amiodarone decreased the heart rate and increased the distance of SV-BA in Zebrafish. Treatment of metoprolol increased the distance of SV-BA in Zebrafish. Conclusions Verapamil, propafenone, metoprolol and amiodarone all could be used to construct zebrafish models of bradycardiac arrhythmia, among which verapamil had the best efficacy. This study proposes the use of anti-arrhythmic drugs, particularly verapamil, to establish the bradycardiac arrhythmia model using zebrafish as well as the corresponding evaluation indicators. This study is of great significance to the research of bradycardiac arrhythmia and its drug development.
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