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.
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The data and materials used to support the findings of this study are available from the corresponding author upon request.
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Hu SY conceived the study and wrote most parts of the manuscript. Zhou Y completed most of the experiments and testing work. Hu ZX provided methodological support in the study design and revised the manuscript. Zhong SJ, Yang M, Huang SM, Li L and Li XC searched and analyzed some literature. All authors have read and approved the manuscript before submission. All authors reviewed the manuscript.
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Supported by Hunan Provincial Natural Science Foundation of China (No. 2020JJ5408), Scientific Research Fund of Hunan Provincial Education Department (No. 21B0361), Research Fund of Hunan University of Chinese Medicine (No. 2019XJJJ012), and Zhuzhou Second Batch of Science and Technology Guidance Projects (No. 2017-17)
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Hu, Sy., Zhou, Y., Zhong, Sj. et al. Shenmai Injection Improves Hypertensive Heart Failure by Inhibiting Myocardial Fibrosis via TGF-β 1/Smad Pathway Regulation. Chin. J. Integr. Med. 29, 119–126 (2023). https://doi.org/10.1007/s11655-022-2899-y
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DOI: https://doi.org/10.1007/s11655-022-2899-y