| 摘要: |
| 目的 探讨微RNA-21（miR-21）能否减轻多柔比星（DOX）心肌毒性，并阐明沉默信息调控因子1（SIRT1）信号通路是否介导其作用。方法 用DOX（1 μmol/L）处理大鼠原代心肌细胞构建DOX心肌毒性模型。将心肌细胞分为8组：对照组、miR-21组、miR-21抑制剂组、DOX组、miR-21+DOX组、miR-21抑制剂+DOX组、Sirtinol+miR-21+DOX组、Sirtinol+DOX组，miR-21 mimics、miR-21抑制剂和Sirtinol（SIRT1抑制剂）分别于DOX处理前24 h加入细胞培养液中。DOX处理24 h后检测心肌细胞的细胞活力、凋亡率、凋亡相关蛋白和SIRT1信号通路表达情况。结果 与对照组相比，DOX处理24 h后心肌细胞活力降低，Bcl-2和SIRT1表达量降低，而Bax和cleaved Caspase-3表达量增加，细胞凋亡率增高，差异均有统计学意义（P<0.05）。与DOX组相比，miR-21可明显提高心肌细胞活力，上调Bcl-2和SIRT1表达，下调Bax和cleaved Caspase-3表达，降低细胞凋亡率，差异均有统计学意义（P<0.05）。抑制SIRT1信号通路可削弱miR-21对心肌细胞的保护作用（P<0.05）。结论 miR-21可通过激活SIRT1信号通路抑制心肌细胞凋亡，提高细胞活力，缓解DOX心肌毒性。 |
| 关键词: 多柔比星 心肌毒性 微RNA-21 沉默信息调控因子1 细胞凋亡 |
| DOI：10.16781/j.0258-879x.2019.04.0386 |
| 投稿时间：2018-12-04修订日期：2019-03-14 |
| 基金项目:国家自然科学基金（81570208）. |
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| MicroRNA-21 attenuates doxorubicin-induced cardiotoxicity by activating silent information regulator 1 signaling pathway |
| GUO Xian1,2,SHI Cheng-yong1,WANG Wen-sheng2,YU Hui1,LI Pan1*,ZHAO Xian-xian1* |
(1. Department of Cardiovasology, Changhai Hospital, Naval Medical University(Second Military Medical University), Shanghai 200433, China;
2. Hospital of PLA No. 95247 Troop, Huizhou 516259, Guangdong, China
*Corresponding authors) |
| Abstract: |
| Objective To explore whether microR-21 (miR-21) can alleviate doxorubicin (DOX)-induced cardiotoxicity and whether silent information regulator 1 (SIRT1) signaling pathway mediates the roles. Methods Neonatal rat cardiac myocytes were treated with DOX (1 μmol/L) to induce DOX myocardial toxicity model. The cardiomyocytes were randomized into 8 groups:control group, miR-21 group, miR-21 inhibitor group, DOX group, miR-21+DOX group, miR-21 inhibitor+DOX group, Sirtinol+miR-21+DOX group and Sirtinol+DOX group. The miR-21 mimics, miR-21 inhibitors and Sirtinol (SIRT1 inhibitor) were given at 24 h before DOX treatment. After treatment with DOX for 24 h, the cell viability, apoptosis rate, and the expression levels of apoptosis-related proteins and SIRT1 signaling pathway were detected. Results Compared with the control group, the cell viability, and the expression levels of Bcl-2 and SIRT1 were significantly decreased in the cardiomyocytes after treatment with DOX for 24 h, while the expression levels of Bax and cleaved Caspase-3, and apoptotic rate were significantly increased (P<0.05). Compared with the DOX group, miR-21 significantly increased cell viability and the expression levels of Bcl-2 and SIRT1, and significantly decreased the expression levels of Bax and cleaved Caspase-3 and apoptotic rate (P<0.05). Inhibiting SIRT1 signaling pathway could significantly weaken the protective effect of miR-21 on cardiomyocytes (P<0.05). Conclusion miR-21 can inhibit cardiomyocyte apoptosis, increase cell viability and alleviate DOX-induced cardiotoxicity by activating SIRT1 signaling pathway. |
| Key words: doxorubicin cardiotoxicity miR-21 silent information regulator 1 cell apoptosis |
