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Copyright (c) 2023 Peng Zhang, Fei Wang, Jia Song, Fangju Su, Yan Liu
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
The undersigned hereby assign all rights, included but not limited to copyright, for this manuscript to CMB Association upon its submission for consideration to publication on Cellular and Molecular Biology. The rights assigned include, but are not limited to, the sole and exclusive rights to license, sell, subsequently assign, derive, distribute, display and reproduce this manuscript, in whole or in part, in any format, electronic or otherwise, including those in existence at the time this agreement was signed. The authors hereby warrant that they have not granted or assigned, and shall not grant or assign, the aforementioned rights to any other person, firm, organization, or other entity. All rights are automatically restored to authors if this manuscript is not accepted for publication.Fasudil attenuates myocardial fibrosis in rats with diabetes mellitus via TGF-β1/Smad signaling pathway
Corresponding Author(s) : Yan Liu
Cellular and Molecular Biology,
Vol. 69 No. 10: Issue 10
Abstract
This research aimed to the study influence of fasudil (FAS) on myocardial fibrosis in rats with diabetes mellitus (DM) via the transforming growth factor-beta 1 (TGF-β1)/ small mothers against decapentaplegic (Smad) signaling pathway. A total of 30 Sprague-Dawley rats were randomly divided into a blank control group (Control group, n=10), DM model group (DM group, n=10) and FAS treatment group (FAS group, n=10), and their blood and myocardial tissues were collected. Then blood glucose (GLU) content, hepatic and myocardial function indexes, ejection fraction (EF) and other cardiac function parameters were detected, and ELISA was employed to determine the content of serum IL-6, IL-1 and TNF-α. The pathological changes and cell apoptosis in myocardial tissues were observed through hematoxylin-eosin (HE) staining combined with terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay. The gene expression levels of Collagen I, α-smooth muscle actin (α-SMA), and the TGFβ1/Smad3 pathway were determined via qRT-PCR, and the expression levels of the pathway-associated proteins were measured via Western blotting. DM group exhibited an increase in GLU level (P<0.05), suggesting successful modeling. The content of serum Fas, aspartate aminotransferase (AST), creatine kinase-MB (CK-MB), IL-6, IL-1 and TNF-α in DM group were higher than those in Control group (P<0.05). The fractional shortening (FS) and EF in DM group were lower than those in Control group (P<0.05), and the left ventricular end-diastolic diameter (LVEDD) and left ventricular end-systolic diameter (LVESD) were distinctly greater than those in Control group (P<0.05). Myocardial cells in Control group were regularly arranged, and DM group exhibited fibrosis in myocardial cells, with a substantial increase in apoptotic myocardial cells (P<0.05). Besides, FAS group showed notable declines in myocardial fibrosis and apoptotic myocardial cells (P<0.05). Gene assay results revealed that the rats in FAS group had markedly lowered levels of Collagen I, α-SMA, TGF-β1 and Smad3 in myocardial tissues (P<0.05), but their expression levels were remarkably raised in DM group (P<0.05). According to the results of Western blotting, the levels of TGF-β1 and Smad3 in rat myocardial tissues were decreased in FAS group (P<0.05), implying that FAS inhibits the expressions of the TGF-β1/Smad signaling pathway and the relevant molecules. FAS can attenuate myocardial fibrosis in DM rats through suppressing the TGF-β1/Smad signaling pathway.
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