Metformin ameliorates cardiac conduction delay by regulating microRNA-1 in mice
Metformin ameliorates cardiac conduction delay by regulating microRNA-1 in mice
复制标题
二甲双胍通过调节 microRNA-1 改善小鼠心脏传导延迟
DOI：
10.1016/j.ejphar.2020.173131
复制
发表时间：
2020
影响因子：
5
通讯作者：
Hongli Shan
中科院分区：
文献类型：
--
作者：
Lifang Lv;Nan Zheng;Lijia Zhang;Ruotong Li;Yingnan Li;Rui Yang;Chao Li;Ruonan Fang;Azaliia Shabanova;Xuelian Li;Yingqi Liu;Haihai Liang;Yuhong Zhou;Hongli Shan
心脏传导延迟可能是几种心脏疾病的常见并发症。少数治疗方法和药物对心脏传导延迟有较好的疗效。蛋氨酸（Met）对心脏有保护作用。本研究的目的是探讨蛋氨酸是否能改善心脏传导延迟及其可能的机制。使用心脏特异性microRNA-1（miR-1）转基因（TG）和心肌梗死（MI）小鼠模型。以胃内方式向小鼠施用Met。我们发现miR-1的表达在H2 O2处理的心肌细胞以及TG和MI小鼠中显著上调。与对照组相比，H2 O2处理的心肌细胞及TG和MI小鼠心肌组织中内向整流钾通道2.1（Kir2.1）和连接蛋白43（CX43）蛋白水平均下调。此外，PR和QT间期延长，动作电位时程（APD）延迟，传导速度（CV）降低，心脏中miR-1上调。同时，MI小鼠心脏出现闰盘损伤。有趣的是，Met可以显著抑制miR-1的上调，并减弱上述变化。综上所述，这表明Met可以通过抑制miR-1表达在改善心脏传导延迟中发挥重要作用。本研究提示Met是治疗心脏传导延迟的潜在候选药物，为药物治疗心律失常提供了新思路。
Cardiac conduction delay may occur as a common complication of several cardiac diseases. A few therapies and drugs have a good effect on cardiac conduction delay. Metformin (Met) has a protective effect on the heart. This study's aim was to investigate whether Met could ameliorate cardiac conduction delay and its potential mechanism. Cardiac-specific microRNA-1 (miR-1) transgenic (TG) and myocardial infarction (MI) mouse models were used. Mice were administered with Met in an intragastric manner. We found that the expression of miR-1 was significantly up-regulated in H2O2treated cardiomyocytes as well as in TG and MI mice. The protein levels of inwardly rectifying potassium channel 2.1 (Kir2.1) and Connexin43 (CX43) were down-regulated both in cardiomyocytes treated with H2O2as well as cardiac tissues of TG and MI mice, as compared to their controls. Furthermore, the PR and QT intervals were prolonged, action potential duration (APD) was delayed, and conduction velocity (CV) was reduced, with upregulation of miR-1 in the hearts. In the meanwhile, intercalated disc injuries were found in the hearts of MI mice. Interestingly, Met can noticeably inhibit miR-1 upregulation and attenuate the changes mentioned above. Taken together, this suggested that Met could play an important role in improving cardiac conduction delay through inhibition of miR-1 expression. Our study proposes that Met is a potential candidate for the treatment of cardiac conduction delay and provides a new idea of treating arrhythmia with a drug.