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

doi:10.16098/j.issn.0529-1356.2018.03.007

解剖学报 ›› 2018, Vol. 49 ›› Issue (3): 309-316.doi: 10.16098/j.issn.0529-1356.2018.03.007

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

崔宁¹ 柯兵兵²吴福建³ 白蕊³刘涛燕³ 李蕾¹兰峰³崔鸣^1*

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

收稿日期:2018-01-04 修回日期:2018-01-15 出版日期:2018-06-06 发布日期:2018-09-18
通讯作者: 崔鸣 E-mail:mingcui@bjmu.edu.cn
基金资助:
自噬相关基因FAM176A调控心脏重塑及其机制的研究

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

CUI Ning¹ KE Bing-bing² WU Fu-jian³ BAI Rui³ LIU Tao-yan³ LI Lei¹ LAN Feng³CUI Ming ^1*

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

Received:2018-01-04 Revised:2018-01-15 Online:2018-06-06 Published:2018-09-18
Contact: CUI Ming E-mail:mingcui@bjmu.edu.cn

摘要/Abstract

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。

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

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.

Key words: Doxorubicin, Cardiotoxicity, Human induced pluripotent stem cell, Cardiomyocyte injury model, Immunofluorescence, Real-time PCR

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.

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.

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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

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