盐酸克伦特罗对人类诱导多能干细胞来源心肌细胞的毒性作用  

Myotoxic Effects of Clenbuterol on Cardiomyocytes Derived from Human Induced Pluripotent Stem Cells

作　　者：杨慧[1] 吴劭一 毛益申 王青洁[1] 刘琛[3] 周奕[2] 孙宁[1] 

机构地区：[1]复旦大学基础医学院生理与病理生理学系 [2]复旦大学老年医学研究中心,上海200032 [3]上海市上海中学,上海200231

出　　处：《微循环学杂志》2015年第4期15-18,24,I0002,I0003,共7页Chinese Journal of Microcirculation

摘　　要：目的:探讨盐酸克伦特罗对人类诱导多能干细胞(iPSC)来源心肌细胞的毒性作用。方法:将人皮肤来源的iPSC成功定向分化为心肌细胞,加入不同浓度盐酸克伦特罗,使之分为对照组(0μg/ml)、1μg/ml组、10μg/ml组、20μg/ml组、50μg/ml组、100μg/ml组等6组(n均=3),相同条件共培养7天后,观察盐酸克伦特罗对心肌细胞形态大小、搏动频率及凋亡率的影响。结果:不同浓度盐酸克伦特罗均可使心肌细胞缩小(P<0.05),50-100μg/ml盐酸克伦特罗可致心肌细胞骨架断裂,甚至呈颗粒状。各种浓度盐酸克伦特罗均致心肌细胞搏动频率加快(P<0.05),且有浓度越高搏动越快的趋势。10μg/ml组和50μg/ml组所致心肌细胞凋亡率显著高于对照组(P<0.05)。结论:盐酸克伦特罗对人类皮肤来源iPSC分化的心肌细胞有毒性作用。Objective：To investigate the toxic effects of clenbuterol hydrochloride （CL）on cardiomyocytes （CMs）derived from human induced pluripotent stem cells （hiPSCs）.Method：Pluripotent stem cells derived from human skin fibroblasts were directly differentiated into CMs.The iPSC-derived CMs （iPSC-CMs）were then ran-domly divided into 6 groups and treated with different concentrations of CL.The cellular structure,beating frequen-cy and apoptosis rates of these iPSC-CMs were evaluated in groups.Results：After CL treatment,iPSC-CMs mor-phologically exhibited a smaller size.Under 50-100μg/ml of CL,myofibers of the iPSC-CMs seemed irregular and exhibited a granular morphology.The beating frequency of iPSC-CMs and CL concentration were positively correla-ted.Compared with the control,the apoptosis rates in iPSC-CMs treated with 10μg/ml and group 50μg/ml were significantly increased.Conclusion：CL has toxic effects on human cardiomyocytes derived from hiPSCs.

关 键 词：盐酸克伦特罗 诱导多能干细胞 心肌细胞 凋亡 

分 类 号：R337[医药卫生—人体生理学]