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Shenmai Injection Improves Hypertensive Heart Failure by Inhibiting Myocardial Fibrosis via TGF-β1/Smad Pathway Regulation
- Chinese Journal of Integrative Medicine Vol. 29, Issue 2, Pages: 119-126(2023)
- Affiliations：
1.School of Sports Art, Hunan University of Chinese Medicine, Changsha (410208), China
2.College of Health Science, Wuhan Sports University, Wuhan (430079), China
3.Department of Medicine, Hunan Traditional Chinese Medical College, Zhuzhou, Hunan Province (412012), China
4.Graduate School, Hunan University of Chinese Medicine, Changsha (410208), China
5.Institute of Chinese Medicine Diagnosis, Hunan University of Chinese Medicine, Changsha(410208), China
- Author bio：
Prof. HU Zhi-xi, E-mail: zhixihu@qq.com
- Funds：
DOI：10.1007/s11655-022-2899-y
CLC：Published：2023-02，
Published Online：15 July 2022，
Accepted：12 January 2022
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HU Si-yuan, ZHOU Yao, ZHONG Sen-jie, et al. Shenmai Injection Improves Hypertensive Heart Failure by Inhibiting Myocardial Fibrosis via TGF-β1/Smad Pathway Regulation. [J]. Chinese Journal of Integrative Medicine 29(2):119-126(2023)
HU Si-yuan, ZHOU Yao, ZHONG Sen-jie, et al. Shenmai Injection Improves Hypertensive Heart Failure by Inhibiting Myocardial Fibrosis via TGF-β1/Smad Pathway Regulation. [J]. Chinese Journal of Integrative Medicine 29(2):119-126(2023) DOI： 10.1007/s11655-022-2899-y.
摘要
目的:
2
研究参麦注射液对高血压心衰的治疗作用及其抑制心肌纤维化的分子机制.
方法:
2
将24只Dahl/SS盐敏感大鼠分为6只正常对照组 (Control) 和18只模型组 (Model)
分别给予含0.3% NaCl的正常饲料和含8% NaCl高盐饲料
还将6只SS-13BN非盐敏感大鼠给予8% NaCl的高盐饲料作为阴性对照组 (Negative control)
观察其血压和心功能变化. 造模完成后
将模型大鼠随机分为心衰组 (HF) 、参麦注射液组 (SMI) 和吡非尼酮组 (PFD)
每组6只
分别给予生理盐水、参麦注射液和吡非尼酮干预. 采用小动物血压计、超声心动图、ELISA、HE染色、Masson染色、免疫荧光和qPCR等方法检测血压、心功能、纤维化及相关分子表达.
结果:
2
高盐喂养后
与Control组和Negative control组相比
Model组大鼠血压升高 (
P
<
0.05)
LVEF和LVFS降低 (
P
<
0.05)
血清NT-proBNP浓度升高 (
P
<
0.05) ; 心肌细胞排列紊乱
水肿严重
心肌纤维化程度加重 (
P
<
0.05) ; Col I蛋白及mRNA表达上调 (
P
<
0.05)
TGF-β1、Smad2和Smad3 mRNA表达上调 (
P
<
0.05) . 而参麦注射液干预后
LVEF和LVFS上升 (
P
<
0.05)
心肌形态改善
胶原容积分数降低 (
P
<
0.05)
Col I、TGF-β1、Smad2、Smad3 mRNA表达及Col I蛋白表达均下调 (
P
<
0.05) .
结论:
2
心肌纤维化是高血压心衰的重要病理特征
参麦注射液可通过调节TGF-β1/Smad信号通路抑制心肌纤维化
有效改善心力衰竭.
Abstract
Objective:
2
To study effects of Shenmai Injection on hypertensive heart failure and its mechanism for inhibiting myocardial fibrosis.
Methods:
2
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:
2
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 β1 (TGF-β1)
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-β1
Smad2 and Smad3
as well as Col Ⅰ protein expression
were all significantly down-regulated (all
P
<
0.05).
Conclusion:
2
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-β1/Smad signaling pathway.
关键词
心肌纤维化心衰参麦注射液TGF-β1/Smad高血压
Keywords
myocardial fibrosisheart failureShenmai Injectiontransforming growth factor β1/smadhypertension
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