Anti-Fibrosis Effect of Relaxin and Spironolactone Combined on Isoprenaline-Induced Myocardial Fibrosis in Rats via Inhibition of Endothelial-Mesenchymal Transition
Anti-Fibrosis Effect of Relaxin and Spironolactone Combined on Isoprenaline-Induced Myocardial Fibrosis in Rats via Inhibition of Endothelial-Mesenchymal Transition
复制标题
松弛素与螺内酯联用抑制内皮-间质转化对异丙肾上腺素诱导的大鼠心肌纤维化的抗纤维化作用
DOI：
10.1159/000464125
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发表时间：
2017-01-01
影响因子：
--
通讯作者：
Zhou, Hao
中科院分区：
文献类型：
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作者：
Cai, Jiejie;Chen, Xiao;Zhou, Hao
背景：松弛素和螺内酯联合应用对心肌纤维化的影响尚未见报道。因此，我们研究了联合治疗对异丙肾上腺素诱导的心肌纤维化的影响及其机制。方法：皮下注射异丙肾上腺素诱导大鼠心肌纤维化，皮下注射松弛素（2 μ g.kg（-1）.d（-1））和螺内酯（30 mg.kg（-1）.d（-1）），连续14天。在体外，在用松弛素（200 ng/ml）和/或螺内酯（1 μ M）预处理的人脐静脉内皮细胞（HUVECs）中，用转化生长因子β（TGF-β）诱导内皮间质转化。结果如下：松弛素和螺内酯单独或联合使用可改善心脏功能，降低心脏重量指数;减少纤维组织增生;降低I型和III型胶原水平;降低平滑肌肌动蛋白（α-SMA）和转化生长因子-β 1（TGF-β 1）的表达，并增加异丙肾上腺素诱导的心肌纤维化大鼠分化簇-31（CD 31）的表达。在体外，与TGF-β治疗相比，松弛素和螺内酯单独使用或与TGF-β联合使用可降低细胞迁移率、α-SMA和波形蛋白水平，但增加血管内皮钙粘蛋白（VE-钙粘蛋白）和内皮CD 31水平。尤其是联合应用，无论在体内还是体外，其效果均优于松弛素和螺内酯单独应用。结论：松弛素和螺内酯联合应用可减轻异丙肾上腺素诱导的大鼠心肌纤维化，其机制可能与抑制心肌内皮间质转化有关。(C)2017作者（S）
Background: The effect of relaxin and spironolactone combined on myocardial fibrosis has not been reported. Thus, we investigated the effect of the combined therapy on isoprenaline-induced myocardial fibrosis and the mechanism. Methods: Rats were injected subcutaneously with isoprenaline to induce myocardial fibrosis and underwent subcutaneous injection with relaxin (2 mu g.kg(-1).d(-1)) and given a gavage of spironolactone (30 mg.kg(-1).d(-1)) alone or combined for 14 days. In vitro, the endothelial mesenchymal transition was induced with transforming growth factor beta (TGF-beta) in human umbilical vein endothelial cells (HUVECs) pretreated with relaxin, 200 ng/ml, and/or spironolactone, 1uM. Results: Relaxin and spironolactone used alone or combined improved cardiac function and decreased cardiac weight indices; reduced fibrous tissue proliferation; reduced levels of type I and III collagen; decreased the expression of a smooth muscle actin (alpha-SMA) and transforming growth factor-beta 1 (TGF-beta 1), and increased the expression of cluster of differentiation-31 (CD31) in rats with isoprenaline-induced myocardial fibrosis. In vitro, compared with TGF-beta treatment, relaxin and spironolactone used alone or combined with TGF-beta decreased cell mobility, a-SMA and vimentin levels but increased vascular endothelial cadherin (VE-cadherin) and endothelial CD31levels. Especially, combined therapy had more remarkable effect than relaxin and spironolactone used alone both in vitro and in vivo. Conclusion: Relaxin and spironolactone combined affected isoprenaline-induced myocardial fibrosis in rats that the mechanism might be inhibition of the cardiac endothelial mesenchymal transition. (C) 2017 The Author(s)