Department of Pharmacology (State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education), Harbin Medical University, Harbin, China.
School of Pharmacy, Jining Medical University, Rizhao, China.
J Pharm Pharmacol. 2020 Jan;72(1):76-83. doi: 10.1111/jphp.13192. Epub 2019 Nov 8.
Metoprolol is regarded as a first-line medicine for the treatment of myocardial infarction (MI). However, the underlying mechanisms remain largely unknown. This study aimed to investigate the involvement of miR-1 in the pharmacological function of metoprolol.
In vivo MI model was established by left anterior descending coronary artery (LAD) ligation. The effects of metoprolol on infarct size and cardiac dysfunction were determined by triphenyltetrazolium chloride staining and cardiac echocardiography, respectively. In vitro oxidative stress cardiomyocyte model was established by H O treatment. The effect of metoprolol on the expression of miR-1 and connexin43 (Cx43) was quantified by real-time PCR and western blot, respectively. The intercellular communication was evaluated by lucifer yellow dye diffusion.
Left anterior descending ligation-induced MI injury was markedly attenuated by metoprolol as shown by reduced infarct size and better cardiac function. Metoprolol reversed the up-regulation of miR-1 and down-regulation of Cx43 in MI heart. Moreover, in H O -stimulated cardiomyocytes, overexpression of miR-1 abolished the effects of metoprolol on Cx43 up-regulation and increased intercellular communication, indicating that miR-1 may be a necessary mediator for the cardiac protective function of metoprolol.
Metoprolol relieves MI injury via suppression miR-1, thus increasing its target protein Cx43 and improving intercellular communication.
美托洛尔被认为是治疗心肌梗死（MI）的一线药物。然而，其潜在机制在很大程度上尚不清楚。本研究旨在探讨 miR-1 在美托洛尔药理学功能中的作用。
通过结扎左前降支冠状动脉（LAD）建立体内 MI 模型。通过氯化三苯基四氮唑（TTC）染色和心脏超声心动图分别测定美托洛尔对梗死面积和心功能障碍的影响。通过 H2O2 处理建立体外氧化应激心肌细胞模型。通过实时 PCR 和 Western blot 分别定量测定美托洛尔对 miR-1 和连接蛋白 43（Cx43）表达的影响。通过荧光黄染料扩散评估细胞间通讯。
左前降支结扎诱导的 MI 损伤明显被美托洛尔减轻，表现为梗死面积减小和心功能改善。美托洛尔逆转了 MI 心脏中 miR-1 的上调和 Cx43 的下调。此外，在 H2O2 刺激的心肌细胞中，miR-1 的过表达消除了美托洛尔对 Cx43 上调的作用，并增加了细胞间通讯，表明 miR-1 可能是美托洛尔心脏保护作用的必要介导物。
美托洛尔通过抑制 miR-1 减轻 MI 损伤，从而增加其靶蛋白 Cx43 并改善细胞间通讯。
