| 郭 显,史承勇,李 攀,刁繁荣,唐文栋,侯 攀,赵仙先.姜黄素预处理通过上调miR-21缓解多柔比星心肌毒性[J].,2019,19(10):1829-1834 |
| 姜黄素预处理通过上调miR-21缓解多柔比星心肌毒性 |
| Curcumin Pretreatment Relieves Doxorubicin-induced Cardiotoxicity through up-regulating miR-21 |
| 投稿时间：2018-11-26 修订日期：2018-12-20 |
| DOI：10.13241/j.cnki.pmb.2019.10.006 |
| 中文关键词: 姜黄素 预处理 多柔比星心肌毒性 miR-21 凋亡 氧化应激 |
| 英文关键词: Curcumin Pretreatment Doxorubicin-induced cardiotoxicity miR-21 Apoptosis Oxidative Stress |
| 基金项目:国家自然科学基金项目（81570208）；上海市卫生系统优秀人才培养计划（2017YQ029） |
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| 中文摘要: |
| 摘要 目的：探究miR-21是否介导姜黄素（Cur）预处理抗多柔比星（DOX）心肌毒性作用。方法：体外分离培养大鼠原代心肌细胞，用DOX处理24 h建立心肌毒性离体模型。姜黄素于DOX处理前12 h加入心肌细胞培养液中。实验分组如下：Control组；Cur组；DOX组；Cur+DOX组；miR-21i（miR-21抑制剂）+Cur+DOX组；miR-21i+DOX组。DOX处理24 h后检测miR-21表达情况、细胞活力、凋亡和氧化应激相关指标。结果：与DOX组相比，姜黄素预处理可呈剂量依赖性地提高DOX处理后心肌细胞活力，且浓度为5 μM时效果最佳。此外，姜黄素预处理可以明显提高Bcl-2和miR-21表达，降低心肌Bax和cleaved Caspase-3表达、凋亡率以及心肌细胞活性氧（ROS）产量和丙二醛（MDA）含量。而用miR-21i下调miR-21表达可明显削弱姜黄素预处理对DOX心肌损伤的上述保护作用（均P < 0.05）。结论：姜黄素预处理可通过上调miR-21表达，缓解心肌凋亡和氧化应激损伤，进而缓解DOX心肌毒性。 |
| 英文摘要: |
| ABSTRACT Objective: To investigate whether miR-21 mediates the cardioprotective effects of curcumin (Cur) pretreatment against doxorubicin (DOX)-induced cardiotoxicity. Methods: Neonatal rat cardiac myocytes (NRCMs) were isolated and cultured in vitro, and then treated with DOX for 24 h to establish the cardiotoxicity model in vitro. Curcumin was added to the culture medium 12 h before DOX treatment. The experiments were grouped as follows: Control group; Cur group; DOX group; Cur+DOX group; miR-21i (miR-21 inhibitor)+Cur+DOX group; and miR-21i+DOX group. The expression of miR-21, cell viability and indicators of apoptosis and oxidative stress were detected 24 h after DOX treatment. Results: Compared with the DOX group, curcumin pretreatment increased the cell viability of DOX-treated NRCMs in a dose-dependent manner, and the optimal concentration was 5 μM. In addition, curcumin pretreatment significantly increased the expression of Bcl-2 and miR-21, and decreased the expression of Bax and cleaved Caspase-3, apoptotic ratio, and the production of reactive oxygen species (ROS) and malondialdehyde (MDA) in NRCMs. Down-regulation of miR-21 expression by miR-21i significantly attenuated the protective effects of curcumin pretreatment on DOX-induced cardiotoxicity mentioned above (all P < 0.05). Conclusion: Curcumin pretreatment can up-regulate the expression of miR-21, thereby alleviating myocardial apoptosis and oxidative stress, and mitigating the cardiotoxicity of DOX. |
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