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补阳还五汤通过抑制 TGF-β/Smads 和 MAPKs 信号通路激活的纤维化缓解压力超负荷诱导的心脏重构。

Buyanghuanwu Decoction alleviated pressure overload induced cardiac remodeling by suppressing Tgf-β/Smads and MAPKs signaling activated fibrosis.

机构信息

Department of Pathology, School of Basic Medical Sciences, Shanghai University of Traditional Chinese Medicine, No. 1200 Cailun Road, Shanghai, 201203, China.

Experimental Center, School of Basic Medical Sciences, Shanghai University of Traditional Chinese Medicine, No. 1200 Cailun Road, Shanghai, 201203, China.

出版信息

Biomed Pharmacother. 2017 Nov;95:461-468. doi: 10.1016/j.biopha.2017.08.102. Epub 2017 Sep 12.

Abstract

Buyanghuanwu Decoction (BHD), a traditional Chinese medicine recipe, is a representative prescription for the treatment of qi-deficiency and blood-stasis syndrome. In this study, the effect of BHD on pressure overload induced cardiac remodeling was investigated and possible mechanism underlying was explored. Rats were randomly divided into four groups: sham, transverse aorta constriction (TAC) with saline, TAC with telmisartan (TAC+Tel), and TAC with BHD (TAC+BHD) for 16 weeks (n=6∼8 in each group). Cardiac morphological and functional changes were evaluated by echocardiography and histological methods, the molecular alterations were detected by western blotting. Our results revealed that pressure overload prominently induced cardiac dysfunction, dilated and atrophied left ventricle, decreased cardiomyocyte cross sectional area, and fibrosis. However, BHD, similar to Tel, greatly reversed cardiac dysfunction, left ventricular dilation, and fibrosis, together with increased left ventricular wall thickness and size of cardiomyocyte. Furthermore, activated classical pro-fibrotic signaling of Tgf-β/Smads and MAPKs after TAC was dramatically suppressed by BHD or Tel treatment. Taken together, it was demonstrated in this study that BHD exerted a cardioprotective effect against pressure overload induced cardiac remodeling via inactivation of Tgf-β/Smads and MAPKs signaling triggered fibrosis.

摘要

补阳还五汤(BHD)是一种治疗气虚血瘀证的中药方剂。本研究旨在探讨 BHD 对压力超负荷诱导的心肌重构的影响及其可能的作用机制。将大鼠随机分为四组:假手术组、盐水处理的腹主动脉缩窄(TAC)组、替米沙坦处理的 TAC 组(TAC+Tel)和 BHD 处理的 TAC 组(TAC+BHD),每组 6~8 只,共 16 周。通过超声心动图和组织学方法评估心脏形态和功能变化,通过 Western blot 检测分子变化。结果表明,压力超负荷显著诱导心脏功能障碍、左心室扩张和萎缩、心肌细胞横截面积减小以及纤维化。然而,BHD 与 Tel 相似,可显著逆转心脏功能障碍、左心室扩张和纤维化,同时增加左心室壁厚度和心肌细胞大小。此外,TAC 后 TGF-β/Smads 和 MAPKs 经典促纤维化信号被 BHD 或 Tel 处理显著抑制。综上所述,本研究表明,BHD 通过抑制 TGF-β/Smads 和 MAPKs 信号触发的纤维化,对压力超负荷诱导的心肌重构发挥心脏保护作用。

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