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参麦注射液通过调节TGF-β 1/Smad信号通路抑制心肌纤维化改善高血压性心力衰竭

Shenmai Injection Improves Hypertensive Heart Failure by Inhibiting Myocardial Fibrosis via TGF-β 1/Smad Pathway Regulation.

作者信息

Hu Si-Yuan, Zhou Yao, Zhong Sen-Jie, Yang Meng, Huang Shu-Min, Li Lin, Li Xin-Chun, Hu Zhi-Xi

机构信息

School of Sports Art, Hunan University of Chinese Medicine, Changsha, 410208, China.

College of Health Science, Wuhan Sports University, Wuhan, 430079, China.

出版信息

Chin J Integr Med. 2023 Feb;29(2):119-126. doi: 10.1007/s11655-022-2899-y. Epub 2022 Jul 15.

DOI:10.1007/s11655-022-2899-y
PMID:35840852
Abstract

OBJECTIVE

To study effects of Shenmai Injection on hypertensive heart failure and its mechanism for inhibiting myocardial fibrosis.

METHODS

Salt-sensitive (Dahl/SS) rats were fed with normal diet (0.3% NaCl) and the high-salt diet (8% NaCl) to observe the changes in blood pressure and heart function, as the control group and the model group. Salt-insensitive rats (SS-13BN) were fed with the high-salt diet (8% NaCl) as the negative control group. After modeling, the model rats were randomly divided into heart failure (HF) group, Shenmai Injection (SMI) group and pirfenidone (PFD) group by a random number table, with 6 rats in each group. They were given sterilized water, SMI and pirfenidone, respectively. Blood pressure, cardiac function, fibrosis and related molecular expression were detected by sphygmomanometer, echocardiogram, enzyme linked immunosorbent assay (ELISA), hematoxylin-eosin staining, Masson staining, immunofluorescence and qPCR analysis.

RESULTS

After high-salt feeding, compared with the control and negative control group, in the model group the blood pressure increased significantly, the left ventricular ejection fraction (LVEF) and left ventricular fraction shortening (LVFS) were significantly reduced, and the serum NT-proBNP concentration increased significantly (all P<0.05); furthermore, the arrangement of myocardial cells was disordered, the edema was severe, and the degree of myocardial fibrosis was also significantly increased (P<0.05); the protein and mRNA expressions of collagen type I (Col I) were up-regulated (P<0.05), and the mRNA expressions of transforming growth factor β 1 (TGF- β 1), Smad2 and Smad3 were significantly up-regulated (P<0.05). Compared with HF group, after intervention of Shenmai Injection, LVEF and LVFS increased, myocardial morphology was improved, collagen volume fraction decreased significantly (P<0.05), and the mRNA expressions of Col I, TGF- β 1, Smad2 and Smad3, as well as Col I protein expression, were all significantly down-regulated (all P<0.05).

CONCLUSION

Myocardial fibrosis is the main pathological manifestation of hypertensive heart failure, and Shenmai Injection could inhibit myocardial fibrosis and effectively improve heart failure by regulating TGF-β 1/Smad signaling pathway.

摘要

目的

研究参麦注射液对高血压性心力衰竭的影响及其抑制心肌纤维化的机制。

方法

将盐敏感型(Dahl/SS)大鼠分别给予正常饮食(0.3%氯化钠)和高盐饮食(8%氯化钠),观察血压和心功能变化,作为对照组和模型组。将盐不敏感型大鼠(SS-13BN)给予高盐饮食(8%氯化钠)作为阴性对照组。造模后,通过随机数字表将模型大鼠随机分为心力衰竭(HF)组、参麦注射液(SMI)组和吡非尼酮(PFD)组,每组6只。分别给予灭菌水、参麦注射液和吡非尼酮。采用血压计、超声心动图、酶联免疫吸附测定(ELISA)、苏木精-伊红染色、Masson染色、免疫荧光和qPCR分析检测血压、心功能、纤维化及相关分子表达。

结果

高盐喂养后,与对照组和阴性对照组相比,模型组血压显著升高,左心室射血分数(LVEF)和左心室缩短分数(LVFS)显著降低,血清NT-proBNP浓度显著升高(均P<0.05);此外,心肌细胞排列紊乱,水肿严重,心肌纤维化程度也显著增加(P<0.05);Ⅰ型胶原(Col I)蛋白和mRNA表达上调(P<0.05),转化生长因子β1(TGF-β1)、Smad2和Smad3的mRNA表达显著上调(P<0.05)。与HF组相比,参麦注射液干预后,LVEF和LVFS升高,心肌形态改善,胶原容积分数显著降低(P<0.05),Col I、TGF-β1、Smad2和Smad3的mRNA表达以及Col I蛋白表达均显著下调(均P<0.05)。

结论

心肌纤维化是高血压性心力衰竭的主要病理表现,参麦注射液可通过调节TGF-β1/Smad信号通路抑制心肌纤维化并有效改善心力衰竭。

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