| 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 |
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| 引用本文： | 崔宁,柯兵兵,吴福建,白蕊,刘涛燕,李蕾,兰峰,崔鸣. 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[J]. 解剖学报, 2018, 49(3): 309-316. DOI: 10.16098/j.issn.0529-1356.2018.03.007 |
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| 作者姓名： | 崔宁 柯兵兵 吴福建 白蕊 刘涛燕 李蕾 兰峰 崔鸣 |
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| 作者单位： | 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 |
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| 基金项目： | 自噬相关基因FAM176A调控心脏重塑及其机制的研究 |
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| 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。
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| 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 |
| 收稿时间： | 2018-01-04 |
| 修稿时间： | 2018-01-15 |
Establishment of doxorubicin induced cardiomyocyte injury model by human induced pluripotent stem cell-derived cardiomyocytes |
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| CUI Ning KE Bing-bing WU Fu-jian BAI Rui LIU Tao-yan LI Lei LAN Feng CUI Ming. Establishment of doxorubicin induced cardiomyocyte injury model by human induced pluripotent stem cell-derived cardiomyocytes[J]. Acta Anatomica Sinica, 2018, 49(3): 309-316. DOI: 10.16098/j.issn.0529-1356.2018.03.007 |
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| Authors: | CUI Ning KE Bing-bing WU Fu-jian BAI Rui LIU Tao-yan LI Lei LAN Feng CUI Ming |
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| Affiliation: | 1.Department of Cardiology, Peking University Third Hospital, Beijing 100191,China;2.Department of Emergency, Beijing Anzhen Hospital, Beijing 100029, China; 3. Beijing Institude of Heart, Lung and Blood Vessel Diseases, Beijing Anzhen Hospital, Capital Medical University, Beijing 100029, China |
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| Abstract: | 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. |
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| Keywords: | Doxorubicin Cardiotoxicity Human induced pluripotent stem cell Cardiomyocyte injury model Immunofluorescence Real-time PCR |
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