Schisandrin A protects against isoproterenol‑induced chronic heart failure via miR‑155

Gao,Lijing; Li,Ting; Li,Shufen; Song,Zhuohui; Chang,Yongli; Yuan,Li

doi:10.3892/mmr.2021.12540

Schisandrin A protects against isoproterenol‑induced chronic heart failure via miR‑155

Authors:
- Lijing Gao
- Ting Li
- Shufen Li
- Zhuohui Song
- Yongli Chang
- Li Yuan
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Affiliations: Medical College, Changzhi Medical College, Changzhi, Shanxi 046000, P.R. China
Published online on: November 22, 2021 https://doi.org/10.3892/mmr.2021.12540
Article Number: 24
Copyright: © Gao et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Schisandrin A (Sch A) has a protective effect on cardiomyocytes. Circulating miR‑155 levels are related to chronic heart failure (CHF). The present study aimed to clarify the role and the molecular mechanism of Sch A in CHF. C57BL/6JGpt mice were used for an isoproterenol (ISO)‑induced CHF model to collect heart samples. Echocardiography was employed to detect heartbeat indicators. The degree of myocardial hypertrophy was evaluated based on the measurement of heart weight (HW), body weight (BW) and tibia length (TL) and the observation using hematoxylin‑eosin staining. Sprague‑Dawley rats were purchased for the separation of neonatal rat ventricular myocytes (NRVMs), which were treated with ISO for 24 h. Transfection regulated the level of miR‑155. The viability of NRVMs was detected via MTT assay. The mRNA and protein levels were measured via reverse transcription‑quantitative PCR and western blotting and immunofluorescence was used to detect the content of α‑smooth muscle actin (α‑SMA). Treatment with ISO resulted in rising left ventricular posterior wall thickness, intra‑ventricular septum diastole, left ventricular end diastolic diameter, left ventricular end systolic diameter, HW/BW, HW/TL and falling ejection fraction and fractional shortening, the trend of which could be reversed by Sch A. Sch A ameliorated myocardial hypertrophy in CHF mice. In addition, Sch A inhibited ISO‑induced upregulated expressions of atrial natriuretic peptide, B‑type natriuretic peptide, B‑myosin heavy chain and miR‑155 in myocardial tissue. Based on the results in vitro, Sch A had no significant effect on the viability of NRVMs when its concentration was <24 µmol/l. Sch A inhibited the levels of miR‑155, α‑SMA and the phosphorylation levels of AKT and cyclic AMP response‑element binding protein (CREB) in ISO‑induced NRVMs, which was reversed by the upregulation of miR‑155. Schisandrin A mediated the AKT/CREB signaling pathway to prevent CHF by regulating the expression of miR‑155, which may shed light on a possible therapeutic target for CHF.

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