阿霉素致人诱导性多潜能干细胞来源的心肌细胞损伤模型的建立  

Establishment of doxorubicin induced cardiomyocyte injury model by human induced pluripotent stem cell-derived cardiomyocytes

作　　者：崔宁[1] 柯兵兵 吴福建 白蕊 刘涛燕 李蕾[1] 兰峰 崔鸣[1] CUI Ning;KE Bing-bing;WU Fu-jian;BAI Rui;LIU Tao-yan;LI Lei;LAN Feng;CUI Ming(Department of Cardiology, Peking University Third Hospital, Beijing 100191, China;Department of Emergency, Belting Anzhen Hospital, Beijing 100029, China;Beijing Instltude of Heart, Lung and Blood Vessel Diseases, Beijing Anzhen Hospital, Capital Medical University, Beijing 100029, China)

机构地区：[1]北京大学第三医院心内科,北京100191 [2]首都医科大学附属北京安贞医院急诊科,北京100029 [3]首都医科大学附属北京安贞医院北京市心肺血管疾病研究所,北京100029

出　　处：《解剖学报》2018年第3期309-316,共8页Acta Anatomica Sinica

基　　金：国家自然科学基金(81570235)

摘　　要：目的利用人诱导性多潜能干细胞来源的心肌细胞(hiPSC-CMs)技术,建立人源的阿霉素心肌细胞损伤模型。方法从人诱导性多潜能干细胞分化hiPSC-CMs,再用不同浓度阿霉素对hiPSC-CMs作用24 h后检测其细胞活性、钙瞬变、氧化应激和DNA损伤等表型。结果阿霉素诱导hiPSC-CMs细胞活力下降,破坏其钙瞬变,引起氧化应激水平上升,导致线粒体膜电位下降和造成DNA损伤,同时右丙亚胺对阿霉素心肌细胞损伤有保护作用。结论利用hiPSC-CMs成功建立了人源阿霉素心肌细胞损伤模型,克服了人心肌细胞难以获得及对药物反应存在种属差异的局限性,更好地用于阿霉素心脏毒性的机制研究及药物筛选。Objective To establish a humanized doxorubicin-induced cardiomyocyte injury model by using human induced pluripotent stem cell-derived cardiomyocytes （hiPSC-CMs）. Methods The human induced pluripotent stem cells were induced to differentiate into hiPSC-CMs. Then the phenotypes of hiPSC-CMs such including cell viability, calcium transients, oxidative stress and DNA damage were detected after treated with various concentrations of doxorubicin for 24 hours. Results Doxorubicin induced a decrease in cell viability of hiPSC-CMs, destroyed calcium transients, increasing oxidative stress, leading to decrease of mitochondrial membrane potential and causing DNA damage, meanwhile dexrazoxane had cardioprotective effects on hiPSC-CMs. Conclusion Doxorubicin induced cardiomyocyte injury model is successfully established with hiPSC-CMs, overcoming the limitation of difficult access to human cardiomyocytes and the different reaction to drug between species, so could to better study on the mechanism of doxorubicin-induced cardiotoxicity and drug screening.

关 键 词：阿霉素 心脏毒性 人诱导性多潜能干细胞 心肌细胞损伤模型 免疫荧光 实时定量聚合酶链反应 

分 类 号：R541.9[医药卫生—心血管疾病] R542.2[医药卫生—内科学]