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

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, ?-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.

SUBMITTER: Mao ZJ

PROVIDER: S-EPMC5856750 | biostudies-literature | 2018 Mar

REPOSITORIES: biostudies-literature

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

Mao Zhu-Jun ZJ Zhang Quan-Long QL Shang Jia J Gao Ting T Yuan Wen-Jun WJ Qin Lu-Ping LP

Scientific reports 20180316 1

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 stu ...[more]

PMID: 29549288

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Project description:Shenfu injection (SFI), a Chinese herbal medicine with substances extracted from Ginseng Radix et Rhizoma Rubra and Aconiti Lateralis Radix Praeparata, is widely used as an anti-inflammatory reagent to treat endotoxin shock in China. However, the mechanism of SFI in endotoxin shock remains to be illuminated. High mobility group box 1 (HMGB1), a vital inflammatory factor in the late stage of endotoxin shock, may stimulate multiple signalling cascades, including ?B (NF-?B), a nuclear transcription factor, as well as tumour necrosis factor (TNF)-? and interleukin (IL)-1?, among others in the overexpression of downstream proinflammatory cytokines. An investigation into the effects of SFI on the inhibition of the HMGB1-NF-?B pathway revealed the contribution of SFI to acute lung injury (ALI) in a rat model of endotoxin shock. To assess the anti-inflammatory activity of SFI, 5?ml/kg, 10?ml/kg, or 15?ml/kg of SFI was administered to different groups of rats following an injection of LPS, and the mean arterial pressure (MAP) at 5?h and the survival rate at 72?h were measured. 24?h after LPS injection, we observed pathological changes in the lung tissue and measured the mRNA expression, production, translocation, and secretion of HMGB1, as well as the expression of the NF-?B signal pathway-related proteins inhibitor of NF-?B (I?B)-?, P50, and P65. We also evaluated the regulation of SFI on the secretion of inflammatory factors including interleukin-1 beta (IL-1?) and TNF-?. SFI effectively prevented the drop in MAP, relieved lung tissue damage, and increased the survival rate in the endotoxin shock model in dose-dependent manner. SFI inhibited the transcription, expression, translocation, and secretion of HMGB1, increased the expression of toll-like receptor (TLR4), increased the production of I?B-?, and decreased the levels of P65, P50, and TNF-? in the lung tissue of endotoxin shock rats in a dose-dependent manner. Furthermore, SFI decreased the secretion of proinflammatory cytokines TNF-? and IL-1?. In summary, SFI improves the survival rate of endotoxin shock, perhaps through inhibiting the HMGB1-NF-?B pathway and thus preventing cytokine storm.

Dataset Information

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

Publications

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

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