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参附注射液通过上调 miR-19a-3p 的表达来减轻大鼠心肌肥厚。

Shenfu Injection attenuates rat myocardial hypertrophy by up-regulating miR-19a-3p expression.

机构信息

Department of Pharmacognosy, Zhejiang Chinese Medical University School of Pharmacy, Hangzhou, 310053, ZJ, China.

Department of Physiology, Ningxia Medical University, Yinchuan, 750004, NX, China.

出版信息

Sci Rep. 2018 Mar 16;8(1):4660. doi: 10.1038/s41598-018-23137-4.

Abstract

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.

摘要

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。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/90ac/5856750/f2e0d42d2912/41598_2018_23137_Fig1_HTML.jpg

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