参麦注射液通过TGF-β1/Smad信号通路抑制心肌纤维化改善高血压心衰

HU Si-yuan; ZHOU Yao; ZHONG Sen-jie; YANG Meng; HUANG Shu-min; LI Lin; LI Xin-chun; HU Zhi-xi

doi:10.1007/s11655-022-2899-y

Your Location：

Home >

Browse articles >

参麦注射液通过TGF-β1/Smad信号通路抑制心肌纤维化改善高血压心衰

Original Article | Updated：2023-02-01

- 参麦注射液通过TGF-β1/Smad信号通路抑制心肌纤维化改善高血压心衰
- Shenmai Injection Improves Hypertensive Heart Failure by Inhibiting Myocardial Fibrosis via TGF-β1/Smad Pathway Regulation
- 中国结合医学杂志（英文版） 2023年29卷第2期页码：119-126
- 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：
  
  Hunan Provincial Natural Science Foundation of China(2020JJ5408);Scientific Research Fund of Hunan Provincial Education Department(21B0361);Research Fund of Hunan University of Chinese Medicine(2019XJJJ012);Zhuzhou Second Batch of Science and Technology Guidance Projects(2017-17)
- DOI：10.1007/s11655-022-2899-y
  中图分类号：
- 纸质出版日期：2023-02，
  
  网络出版日期：2022-07-15，
  
  录用日期：2022-01-12
Scan for full text
参麦注射液通过TGF-β1/Smad信号通路抑制心肌纤维化改善高血压心衰[J]. 中国结合医学杂志（英文版）, 2023,29(2):119-126.

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, 2023,29(2):119-126.
参麦注射液通过TGF-β1/Smad信号通路抑制心肌纤维化改善高血压心衰[J]. 中国结合医学杂志（英文版）, 2023,29(2):119-126. DOI： 10.1007/s11655-022-2899-y.

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, 2023,29(2):119-126. DOI： 10.1007/s11655-022-2899-y.

摘要

目的:

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:

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:

高盐喂养后

与Control组和Negative control组相比

Model组大鼠血压升高 (

0.05)

LVEF和LVFS降低 (

0.05)

血清NT-proBNP浓度升高 (

0.05) ; 心肌细胞排列紊乱

水肿严重

心肌纤维化程度加重 (

0.05) ; Col I蛋白及mRNA表达上调 (

0.05)

TGF-β1、Smad2和Smad3 mRNA表达上调 (

0.05) . 而参麦注射液干预后

LVEF和LVFS上升 (

0.05)

心肌形态改善

胶原容积分数降低 (

0.05)

Col I、TGF-β1、Smad2、Smad3 mRNA表达及Col I蛋白表达均下调 (

0.05) .

结论:

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:

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

0.05); furthermore

the arrangement of myocardial cells was disordered

the edema was severe

and the degree of myocardial fibrosis was also significantly increased (

0.05); the protein and mRNA expressions of collagen type Ⅰ (Col Ⅰ) were up-regulated (

0.05)

and the mRNA expressions of transforming growth factor β1 (TGF-β1)

Smad2 and Smad3 were significantly up-regulated (

0.05). Compared with HF group

after intervention of Shenmai Injection

LVEF and LVFS increased

myocardial morphology was improved

collagen volume fraction decreased significantly (

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

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-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

references

World Health Organization: About cardiovascular diseases.https://www.who.int/cardiovascular_diseases/about_cvd/en/https://www.who.int/cardiovascular_diseases/about_cvd/en/(2019). Accessed.

Tanai E, Frantz S. Pathophysiology of heart failure. Compr Physiol 2015;6:187-214.

Zhou Y, Zhong SJ, Hu SY, Dong WB, Yao T, Liang H, et al.Comparison of the effects of Shenfu Injection and Shenmai Injection on doxorubicin-induced chronic heart failure in rats. Int J Clin Exp Med 2018;11:13169-13179.

Li YM, Wang LL, Dong ZH, Wang SY, Qi LL, Cho K, et al.Cardioprotection of salvianolic acid B and ginsenoside Rg1 combination on subacute myocardial infarction and the underlying mechanism. Phytomedicine 2019;57:255-261.

Zheng X, Wang S, Zou XM, Jing YT, Yang RL, Li SQ, et al.Ginsenoside Rb1 improves cardiac function and remodeling in heart failure. Exp Anim 2017;66:217-228.

Liu XM, Jiang YC, Fu WW, Yu XF, Sui DY. Combination of the ginsenosides Rb3 and Rb2 exerts protective effects against myocardial ischemia reperfusion injury in rats. Int J Mol Med 2020;45:519-531.

Zhang K, Zhang JY, Wang XR, Wang L, Pugliese M, Passantino A, et al. Cardioprotection of Sheng Mai Yin a classic formula on adriamycin induced myocardial injury in Wistar rats. Phytomedicine 2018;38:1-11.

World Medical Association, American Physiological Society.Guiding principles for research involving animals and human beings. Am J Physiol Regul Integr Comp Physiol 2002;283:R281-283.

Boluyt MO, Bing OH, Lakatta EG. The ageing spontaneously hypertensive rat as a model of the transition from stable compensated hypertrophy to heart failure. Eur Heart J 1995;16 Suppl N:19-30.

Houser SR, Margulies KB, Murphy AM, Spinale FG, Francis GS, Prabhu SD, et al. Animal models of heart failure: a scientific statement from the American Heart Association.Circ Res 2012;111:131-150.

Klotz S, Hay I, Zhang GP, Maurer M, Wang J, Burkhoff D.Development of heart failure in chronic hypertensive Dahl rats: focus on heart failure with preserved ejection fraction.Hypertension 2006;47:901-911.

Yamamoto M, Ishizu T, Seo Y, Suto Y, Sai S, Xu DZ, et al.Teneligliptin prevents cardiomyocyte hypertrophy, fibrosis, and development of hypertensive heart failure in Dahl salt-sensitive rats. J Card Fail 2018;24:53-60.

Pfeffer MA. Heart failure and hypertension: importance of prevention. Med Clin North Am 2017;101:19-28.

Kannan A, Janardhanan R. Hypertension as a risk factor for heart failure. Curr Hypertens Rep 2014;16:447.

Messerli FH, Rimoldi SF, Bangalore S. The transition from hypertension to heart failure: contemporary update. JACC Heart Fail 2017;5:543-551.

The Criteria Committee of the New York Heart Association. Nomenclature and criteria for diagnosis of diseases of the heart and great vessels. Little Brown, Boston, Mass, USA; 1994.

Jessup M, Brozena S. Heart failure. N Engl J Med 2003;348:2007-18.

Januzzi JL, Jr., Camargo CA, Anwaruddin S, Baggish AL, Chen AA, Krauser DG, et al. The N-terminal pro-BNP investigation of dyspnea in the emergency department (PRIDE) study. Am J Cardiol 2005;95:948-954.

Chinese Medical Association, Chinese Medical Journals Publishing House, Chinese Society of General Practice, Editorial Board of Chinese Journal of General Practitioners of Chinese Medical Association, Expert Group of Guidelines for Primary Care of Cardiovascular Disease. Guideline for primary care of acute heart failure. Chin J Gen Pract 2019;18:925-930.

Li J, Zhang YH, Wang F, Liu B, Li H, Tang GD, et al. Cardiac damage in patients with the severe type of coronavirus disease 2019 (COVID-19). BMC Cardiovasc Disord 2020;20:479.

Moncrieff J, Lindsay MM, Dunn FG. Hypertensive heart disease and fibrosis. Curr Opin Cardiol 2004;19:326-331.

Xie J, Tu T, Zhou SH, Liu QM. Transforming growth factor (TGF)-β1 signal pathway: A promising therapeutic target for attenuating cardiac fibrosis. Int J Cardiol 2017;239:9.

Kamato D, Burch ML, Piva TJ, Rezaei HB, Rostam MA, Xu SW, et al. Transforming growth factor-β signalling: role and consequences of Smad linker region phosphorylation.Cell Signal 2013;25:2017-2024.

Goumans MJ, Ten Dijke P. TGF-β signaling in control of cardiovascular function. Cold Spring Harb Perspect Biol 2018;10:a022210.

Shi LW, Xie YM, Liao X, Chai Y, Luo YH. Shenmai Injection as an adjuvant treatment for chronic cor pulmonale heart failure: a systematic review and meta-analysis of randomized controlled trials. BMC Complement Altern Med 2015;15:418.

Lu LY, Zheng GQ, Wang Y. An overview of systematic reviews of shenmai injection for healthcare. Evid Based Complement Alternat Med 2014;2014:840650.

Karmazyn M, Gan XT. Treatment of the cardiac hypertrophic response and heart failure with ginseng, ginsenosides, and ginseng-related products. Can J Physiol Pharmacol 2017;95:1170-1176.

Ma J, Ma SY, Yin CX, Wu HL. Shengmai San-derived herbal prevents the development of a vulnerable substrate for atrial fibrillation in a rat model of ischemic heart failure.Biomed Pharmacother 2018;100:156-167.

Dobaczewski M, Chen W, Frangogiannis NG. Transforming growth factor (TGF)-β signaling in cardiac remodeling. J Mol Cell Cardiol 2011;51:600-606.

Cicero AFG, Colletti A. Nutraceuticals and dietary supplements to improve quality of life and outcomes in heart failure patients. Curr Pharm Des 2017;23:1265-1272.

Schichtel M, Wee B, Perera R, Onakpoya I. The effect of advance care planning on heart failure: a systematic review and meta-analysis. J Gen Intern Med 2020;35:874-884.

Graziani F, Varone F, Crea F, Richeldi L. Treating heart failure with preserved ejection fraction: learning from pulmonary fibrosis. Eur J Heart Fail 2018;20:1385-1391.

Kasahara K, Rey FE. The emerging role of gut microbial metabolism on cardiovascular disease. Curr Opin Microbiol 2019;50:64-70.

Burlacu A, Siriopol D, Voroneanu L, Nistor I, Hogas S, Nicolae A, et al. Atherosclerotic renal artery stenosis prevalence and correlations in acute myocardial infarction patients undergoing primary percutaneous coronary interventions: data from nonrandomized single-center study (REN-ACS)—a single center, prospective, observational study. J Am Heart Assoc 2015;4:e002379.

Guan H, Dai GH, Gao WL, Zhang T, Sun C, Ren LL, et al.Effect of Shenmai Injection on long-term prognosis of patients with chronic heart failure: a multicenter, large sample capacity, long-term follow-up retrospective cohort study. Chin J Integr Med 2022;28:312-318.

Wang SM, Ye LF, Wang LH. Shenmai Injection improves energy metabolism in patients with heart failure: a randomized controlled trial. Front Pharmacol 2020;11:459.

Yu JH, Li YH, Liu XY, Ma Z, Michael S, Orgah JO, et al.Mitochondrial dynamics modulation as a critical contribution for Shenmai injection in attenuating hypoxia/reoxygenation injury. J Ethnopharmacol 2019;237:9-19.

More>

浏览量

Downloads

CSCD

文章被引用时，请邮件提醒。

Submit

工具集

关联资源

Involvement of Interleukin-1β/Insulin-Like Growth Factor 1 in Ameliorating Effects of Electroacupuncture on Myocardial Fibrosis Induced by Essential Hypertension