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过表达肾上腺髓质素的间充质干细胞通过抗纤维化作用改善心力衰竭大鼠的心功能。

Mesenchymal stem cells overexpressing adrenomedullin improve heart function through antifibrotic action in rats experiencing heart failure.

机构信息

Department of Cardiology, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150086, P.R. China.

Department of Cardiology, The Third Affiliated Hospital, Harbin Medical University, Harbin, Heilongjiang 150086, P.R. China.

出版信息

Mol Med Rep. 2018 Jan;17(1):1437-1444. doi: 10.3892/mmr.2017.8049. Epub 2017 Nov 14.

Abstract

Previous studies of the authors have indicated that the transplantation of mesenchymal stem cells (MSCs) can attenuate cardiac fibrosis through the secretion of antifibrotic factors, such as adrenomedullin (ADM). Therefore, the authors addressed the hypothesis that ADM overexpression could enhance the antifibrotic effect of MSCs transplantation in a rat model of heart failure. The results of the present study demonstrated that, compared with the group that received the GFP‑MSCs, the transplantation of ADM‑MSCs significantly improved heart function and decreased the percentage of fibrotic area and the expression of matrix metalloproteinase 2. In addition, fluorescence microscopy indicated that the survival of transplanted MSCs also increased significantly in the ADM‑MSCs‑treated group. Furthermore, the expression of fibrosis‑related genes, such as ADM and hepatocyte growth factor, were significantly influenced in the ADM‑MSCs‑treated group. Based on these findings, it may be concluded that, compared with MSCs, MSCs overexpressing ADM can further improve heart function in rats experiencing heart failure through enhanced antifibrotic activity.

摘要

先前的研究表明,间充质干细胞(MSCs)的移植可以通过分泌抗纤维化因子(如肾上腺髓质素(ADM))来减轻心肌纤维化。因此,作者提出假设,即 ADM 的过表达可以增强 MSC 移植在心力衰竭大鼠模型中的抗纤维化作用。本研究结果表明,与接受 GFP-MSCs 的组相比,ADM-MSCs 的移植显著改善了心脏功能,降低了纤维化面积的百分比和基质金属蛋白酶 2 的表达。此外,荧光显微镜观察表明,ADM-MSCs 处理组中移植 MSC 的存活率也显著增加。此外,ADM-MSCs 处理组中纤维化相关基因(如 ADM 和肝细胞生长因子)的表达也受到显著影响。基于这些发现,可以得出结论,与 MSCs 相比,过表达 ADM 的 MSCs 可以通过增强抗纤维化活性,进一步改善心力衰竭大鼠的心脏功能。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d7f7/5780080/a285bcbe1acf/MMR-17-01-1437-g00.jpg

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