Department of Pharmacognosy, Zhejiang Chinese Medical University School of Pharmacy, Hangzhou, 310053, ZJ, China.
Department of Physiology, Ningxia Medical University, Yinchuan, 750004, NX, China.
Sci Rep. 2018 Mar 16;8(1):4660. doi: 10.1038/s41598-018-23137-4.
Shenfu Injection (SFI) is a classical Chinese medicine used to treat heart failure. Our previous study demonstrated that miRNAs underwent changes in rats with myocardial hypertrophy induced by abdominal aortic constriction. Interestingly, there was a significant change in miR-19a-3p, whose target gene is known to be associated with MEF2 signaling. However, whether and how SFI regulates miR-19a-3p in the treatment of myocardial hypertrophy has not been investigated. The purpose of the present study was to investigate the regulatory effect of SFI on miR-19a-3p in MEF2 signaling in the rat hypertrophic myocardium. We found that the miR-19a-3p expression level was significantly decreased in the hypertrophic myocardium, and MEF2A was the target gene of miR-19a-3p. The protein expressions of MEF2A, β-MHC, BNP and TRPC1 were significantly increased in hypertrophic cardiomyocytes. MiR-19a-3p was up-regulated after SFI treatment, and the protein expressions of these genes were significantly decreased. In addition, miR-19a-3p over-expression in hypertrophic cardiomyocytes could decrease MEF2A mRNA and protein expressions, and anti-miR-19a-3p showed the opposite result. Our study provided substantial evidence that miR-19a-3p played a functional role in MEF2 signaling in myocardial hypertrophy. SFI attenuated cardiomyocyte hypertrophy probably through up-regulating or maintaining the miR-19a-3p levels and regulating the MEF2 signaling pathway.
参附注射液(SFI)是一种用于治疗心力衰竭的经典中药。我们之前的研究表明,在腹主动脉缩窄诱导的大鼠心肌肥厚模型中,miRNAs 发生了变化。有趣的是,miR-19a-3p 发生了显著变化,其靶基因已知与 MEF2 信号有关。然而,SFI 是否以及如何调节心肌肥厚中的 miR-19a-3p 尚未得到研究。本研究旨在探讨 SFI 对大鼠肥厚心肌中 MEF2 信号 miR-19a-3p 的调节作用。我们发现,miR-19a-3p 在肥厚心肌中的表达水平显著降低,MEF2A 是 miR-19a-3p 的靶基因。在肥厚心肌细胞中,MEF2A、β-MHC、BNP 和 TRPC1 的蛋白表达显著增加。SFI 处理后 miR-19a-3p 表达上调,这些基因的蛋白表达显著降低。此外,在肥厚心肌细胞中过表达 miR-19a-3p 可降低 MEF2A mRNA 和蛋白表达,而抗 miR-19a-3p 则表现出相反的结果。本研究提供了充分的证据表明,miR-19a-3p 在心肌肥厚中的 MEF2 信号中发挥了功能作用。SFI 可能通过上调或维持 miR-19a-3p 水平并调节 MEF2 信号通路来减轻心肌细胞肥大。