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Journal of Traditional Chinese Medicine >

2022 , Vol. 42 >Issue 5: 764 - 772

DOI: https://doi.org/10.19852/j.cnki.jtcm.20220519.003

Research Articles

Shunxin decoction (顺心组方) improves diastolic function in rats with heart failure with preserved ejection fraction induced by abdominal aorta constriction through cyclic guanosine monophosphate-dependent protein kinase Signaling Pathway

  • Jiaying ZHANG ,
  • Xiangxiang WEI ,
  • Xuefeng LI ,
  • Yang YUAN ,
  • Yinghuan DOU ,
  • Yanbin SHI ,
  • Ping XIE ,
  • Mengru ZHOU ,
  • Junnan ZHAO ,
  • Miao LI ,
  • Shuwen ZHANG ,
  • Rui ZHU ,
  • Ying TIAN ,
  • Hao TAN ,
  • Feifei TIAN
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  • 1 School of basic medical sciences, Institute of Integrated Chinese and Western Medicine,Lanzhou University, Lanzhou 730000, China
    2 Department of Cardiology, Gansu Provincial hospital, Lanzhou 730000, China
Dr. LI Xuefeng, School of basic medical sciences, Lanzhou University, Lanzhou 730000, China. lixuefeng@lzu.du.cn Telephone: +86-931-8915092

Received date: 2021-07-22

  Accepted date: 2021-10-12

  Online published: 2022-05-19

Supported by

Lanzhou Science and Technology Planning Project: Study on a New Traditional Chinese Herb Preparation for Treating HFpEF (No. 2017-4-125) and Belt and Road Special Project of Lanzhou University: Study on Countermeasures of Gansu Traditional Chinese Medicine Industry Entering Five Central Asian Countries(2018ldbrzd004)

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Abstract

OBJECTIVE: To determine whether Shunxin decoction (顺心组方) improves diastolic function in rats with heart failure with preserved ejection fraction (HFpEF) by regulating the cyclic guanosine monophosphate-dependent protein kinase (cGMP-PKG) signaling pathway.

METHODS: Except for control group 8 and sham surgery group 8, the remaining 32 male Sprague-Dawlay rats were developed into HFpEF rat models using the abdominal aorta constriction method. These rats in the HFpEF model were randomly divided into the model group, the Shunxin high-dose group, the Shunxin low-dose group, and the Qiliqiangxin capsule group. The three groups received high-dose Shunxin decoction, low-dose Shunxin decoction, and Qiliqiangxin capsule by gavage, respectively, for 14 d. After the intervention, the diastolic function of each rat was evaluated by testing E/A, heart index, hematoxylin-eosin staining, Masson, myocardial ultrastructure, and N-terminal pro-brain natriuretic peptide (NT-proBNP). The Bioinformatics Analysis Tool for Molecular Mechanism of Traditional Chinese Medicine (BATMAN-TCM) software was used to predict targets for which Shunxin decoction acts on the cGMP-PKG pathway. Natriuretic peptide receptor A (NPRA) and guanylate cyclase (GC) were detected by immunohistochemistry, and eNOS, phosphodiesterase 5A (PDE5A), and cGMP-dependent protein kinase 1(PKG I) were determined by Western blotting.

RESULTS: Compared to the model group, the thickness of the interventricular septum at the end of diastole (IVSd) and the thickness of the posterior wall at the end of diastole (PWd) of the Shunxin decoction high-dose group, Shunxin decoction low-dose group, and Qiliqiangxin capsule group were all significantly reduced (P < 0.01). Furthermore, Shunxin decoction high-dose group E/A value was decreased (P < 0.01). Compared to the model group, the expression of NPRA and GC increased in the Shunxin decoction low-dose group and the Qiliqiangxin capsule group (P < 0.01). Compared to the model group, the expressions of eNOS and PKG I increased (P < 0.05) in the Shunxin decoction high-dose group. The expression of PDE5A expression decreased in the myocardium of the Shunxin decoction high-dose group, Shunxin decoction low-dose group, and Qiliqiangxin capsule group compared to the model group (P < 0.01).

CONCLUSIONS: Shunxin decoction can improve diastolic function in rats with HFpEF. It increases the expression of NPRA, GC, and eNOS in the myocardial cell cGMP-PKG signaling pathway, upregulates cGMP expression, decreases PDE5A expression to reduce the cGMP degradation. Thus, the cGMP continually stimulates PKG I, reversing myocardial hypertrophy and improving myocardial compliance in HFpEF rats.

Key words： heart failure; preserved ejection fraction; diastole; cyclic GMP-dependent protein kinases; signal transduction; Shunxin decoction

Cite this article

Jiaying ZHANG , Xiangxiang WEI , Xuefeng LI , Yang YUAN , Yinghuan DOU , Yanbin SHI , Ping XIE , Mengru ZHOU , Junnan ZHAO , Miao LI , Shuwen ZHANG , Rui ZHU , Ying TIAN , Hao TAN , Feifei TIAN . Shunxin decoction (顺心组方) improves diastolic function in rats with heart failure with preserved ejection fraction induced by abdominal aorta constriction through cyclic guanosine monophosphate-dependent protein kinase Signaling Pathway[J]. Journal of Traditional Chinese Medicine, 2022 , 42(5) : 764 -772 . DOI: 10.19852/j.cnki.jtcm.20220519.003

References

1. Ponikowski P, Voors AA, Anker SD, et al. 2016 ESC guidelines for the diagnosis and treatment of acute and chronic heart failure: the task force for the diagnosis and treatment of acute and chronic heart failure of the european society of Cardiology (ESC). Developed with the special contribution of the heart failure association (HFA) of the ESC. Eur J Heart Fail 2016; 18: 891-975.
2. van Heerebeek L, Paulus WJ. Understanding heart failure with preserved ejection fraction: where are we today? Neth Heart J 2016; 24: 227-36.
3. Yancy CW, Jessup M, Bozkurt B, et al. 2013 ACCF/AHA guideline for the management of heart failure: a report of the american college of cardiology foundation/American heart association task force on practice guidelines. J Am Coll Cardiol 2013; 62: e147-239.
4. Silberman GA, Fan TH, Liu H, et al. Uncoupled cardiac nitric oxide synthase mediates diastolic dysfunction. Circulation 2010; 121: 519-28.
5. Xu Q, Liu HJ, Liu XH. Meta-analysis on the therapeutic effect of Qiliqiangxin capsule in the treatment of heart failure with preserved ejection fraction. Yi Nan Bing Za Zhi 2015; 14: 898-901.
6. Wang J, Yang R, Zhang F, et al. The effect of Chinese herbal medicine on quality of life and exercise tolerance in heart failure with preserved ejection fraction: a systematic review and Meta-analysis of randomized controlled trials. Front Physiol 2018; 9: 1420.
7. Dou Y, Li X, Shi Y, et al. Preparation, optimization and in vitro-in vivo evaluation of Shunxin sustained release granules. Chin Med 2019; 14: 36.
8. Ku HC, Su MJ. DPP 4 deficiency preserved cardiac function in abdominal aortic banding rats. PLoS One 2014; 9: e85634.
9. Németh BT, Mátyás C, Oláh A, et al. Cinaciguat prevents the development of pathologic hypertrophy in a rat model of left ventricular pressure overload. Sci Rep 2016; 6: 37166.
10. LeWinter MM, Meyer M. Mechanisms of diastolic dysfunction in heart failure with a preserved ejection fraction: If it's not one thing it's another. Circ Heart Fail 2013; 6: 1112-5.
11. van Heerebeek L, Hamdani N, Falcão-Pires I, et al. Low myocardial protein kinase G activity in heart failure with preserved ejection fraction. Circulation 2012; 126: 830-9.
12. Frantz S, Klaiber M, Baba HA, et al. Stress-dependent dilated cardiomyopathy in mice with cardiomyocyte-restricted inactivation of cyclic GMP-dependent protein kinase I. Eur Heart J 2013; 34: 1233-44.
13. Nanayakkara S, Kaye DM. Targets for heart failure with preserved ejection fraction. Clin Pharmacol Ther 2017; 102: 228-37.
14. Mohammed SF, Hussain S, Mirzoyev SA, Edwards WD, Maleszewski JJ, Redfield MM. Coronary microvascular rarefaction and myocardial fibrosis in heart failure with preserved ejection fraction. Circulation 2015; 131: 550-9.
15. Takimoto E, Champion HC, Li M, et al. Chronic inhibition of cyclic GMP phosphodiesterase 5a prevents and reverses cardiac hypertrophy. Nat Med 2005; 11: 214-22.
16. Takimoto E. Cyclic GMP-dependent signaling in cardiac myocytes. Circ J 2012; 76: 1819-25.
17. Hou J, Kang YJ. Regression of pathological cardiac hypertrophy: signaling pathways and therapeutic targets. Pharmacol Ther 2012; 135: 337-54.
18. Liu Y, Xu W, Xiong Y, Du G, Qin X. Evaluations of the effect of huangqi against heart failure based on comprehensive echocardiography index and metabonomics. Phytomedicine 2018; 50: 205-12.
19. Lin XP, Cui HJ, Yang AL, Luo JK, Tang T. Astragaloside IV improves vasodilatation function by regulating the PI3K/Akt/ eNOS signaling pathway in rat aorta endothelial cells. J Vasc Res 2018; 55: 169-76.
20. Nizamutdinova IT, Jin YC, Kim JS, et al. Paeonol and paeoniflorin, the main active principles of paeonia albiflora, protect the heart from myocardial ischemia/reperfusion injury in rats. Planta Med 2008; 74: 14-8.
21. Xin QQ, Yang BR, Zhou HF, et al. Paeoniflorin Promotes Angiogenesis in a Vascular Insufficiency model of zebrafish in vivo and in human umbilical vein endothelial cells in vitro. Chin J Integr Med 2018; 24: 494-501.
22. Guo M, Liu Y, Shi D. Cardiovascular actions and therapeutic potential of tetramethylpyrazine (active component isolated from rhizoma chuanxiong): roles and mechanisms. Biomed Res Int 2016; 2016: 2430329.
23. Wang Y, Guo G, Yang BR, et al. Synergistic effects of chuanxiong-chishao herb-pair on promoting angiogenesis at network pharmacological and pharmacodynamic levels. Chin J Integr Med 2017; 23: 654-62.
24. Gao Y, Zhang K, Zhu F, et al. Salvia miltiorrhiza (Danshen) inhibits L-type calcium current and attenuates calcium transient and contractility in rat ventricular myocytes. J Ethnopharmacol 2014; 158 Pt A: 397-403.
25. Wang L, Yu J, Fordjour PA, et al. Danshen injection prevents heart failure by attenuating post-infarct remodeling. J Ethnopharmacol 2017; 205: 22-32.
26. Lü M, Wang TY, Tian XX, et al. Interaction of anti-thrombotic and anti-inflammatory activities of commonly used Traditional Chinese Medicine for promoting blood circulation and removing blood stasis revealed by network pharmacology analysis. Yao Xue Xue Bao 2015; 50: 1135-41.
27. Guan J, Wang Q, Sun Y, et al. Simultaneous determination of two active components in glycyrrhiza uralensis fisch. and its processed products by UFLC. Jilin Yi Yao Xue Yuan Xue Bao 2018; 39: 241-3.
28. Du D, Yan J, Ren J, et al. Synthesis, biological evaluation, and molecular modeling of glycyrrhizin derivatives as potent high-mobility group box-1 inhibitors with anti-heart-failure activity in vivo. J Med Chem 2013; 56: 97-108.
29. Chen HH, Zhao P, Tian J, et al. The effects of Guizhi Gancao decoction on pressure overload-induced heart failure and posttranslational modifications of tubulin in mice. Evid Based Complement Alternat Med 2017; 2017: 2915247.
30. Senni M, Greene SJ, Butler J, Fonarow GC, Gheorghiade M. Drug development for heart failure with preserved ejection fraction: what pieces are missing from the puzzle? Can J Cardiol 2017; 33: 768-76.
31. Tsai EJ, Liu Y, Koitabashi N, et al. Pressure-overload-induced subcellular relocalization/oxidation of soluble guanylyl cyclase in the heart modulates enzyme stimulation. Circ Res 2012; 110: 295-303.
32. Zhang M, Takimoto E, Hsu S, et al. Myocardial remodeling is controlled by myocyte-targeted gene regulation of phospho-diesterase type 5. J Am Coll Cardiol 2010; 56: 2021-30.
33. Borlaug BA, Lewis GD, McNulty SE, et al. Effects of sildenafil on ventricular and vascular function in heart failure with preserved ejection fraction. Circ Heart Fail 2015; 8: 533-41.
34. Hammond J, Balligand JL. Nitric oxide synthase and cyclic GMP signaling in cardiac myocytes: from contractility to remodeling. J Mol Cell Cardiol 2012; 52: 330-40.
35. Tao L, Shen S, Fu S, et al. Traditional Chinese Medication Qiliqiangxin attenuates cardiac remodeling after acute myocardial infarction in mice. Sci Rep 2015; 5: 8374.
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