Abstract
Objective
To evaluate the effects of Huoxin Pill (活心丸, HXP) on cardiac fibrosis and heart failure (HF) in isoproterenol (ISO)-induced HF rats.
Methods
Thirty Wistar rats were randomly divided into 5 groups including control, HF, isosorbide mononitrate (ISMN), HXP low (HXP-L), and HXP high (HXP-H) groups (n=6 for each group) according to the complete randomization method. Rats were pretreated with ISMN (5 mg/kg daily), low concentration of HXP (10 mg/kg daily) or high concentration of HXP (30 mg/kg daily) or equal volume of saline by intragastric administration for 1 week, followed by intraperitoneal injection of ISO (10 mg/kg, 14 days), and continually intragastric administrated with above medicines or saline for additional 6 weeks. The effects of HXP treatment on the cardiac function, heart weight index (HWI), pathological changes, and collagen content were further assessed. Moreover, the role of HXP on activation of transforming growth factor- β 1 (TGF-β 1)/Smads pathway was further explored using immunohistochemistry (IHC) and Western-blot assay.
Results
HXP treatment significantly alleviated the decrease of ejection fraction (EF) and fractional shortening (FS), while decreased the elevation of left ventricular end-systolic volume (LVESV) in ISO-induced HF rats (P<0.05). Moreover, HXP treatment obviously attenuated the increase of HWI and serum level of creatine kinase MB (CK-MB, P<0.05), as well as pathological changes in ISO-induced HF rats. Further determination indicated that HXP treatment alleviated the elevation of collagen I and collagen III protein expression in cardiac tissues of ISO-induced HF rats. Furthermore, HXP treatment significantly down-regulated the increase of TGF-β 1 and p-Smad2/3 protein expression in cardiac tissues of HF rats (P<0.05), while did not affect the expression of total Smad2/3.
Conclusions
HXP attenuated heart failure and cardiac fibrosis in ISO-induced HF rats by suppression of TGF-β 1/Smad2/3 pathway.
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Authors and Affiliations
Contributions
Chu JF and Peng MZ conceived and designed the experiments. Peng MZ, Yang ML, Shen AL and Zhou XL created the models. Lu Y and Shen ZQ performed the experiments. Huang B analyzed the data. Li Q contributed reagents/materials/analysis tools. Peng MZ drafted the manuscript. Chu JF and Peng J revised the manuscript.
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Conflict of Interest
HXP in this study was presented by Youcare Biopharmaceutics Co., Ltd., and LI Qi is the marketing director of the company. There is no potential conflict of interest among other authors.
Supported by the National Natural Science Foundation of China (No. 81774135 and No. 81302884), Science and Technology Major Project of Fujian Province (No. 2019YZ014004), Natural Science Foundations of Fujian Province (No. 2018J01884), and Fujian Provincial Health and Family Planning Commission (No. 2018-CX-42)
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Peng, Mz., Yang, Ml., Shen, Al. et al. Huoxin Pill (活心丸) Attenuates Cardiac Fibrosis by Suppressing TGF-β1/Smad2/3 Pathway in Isoproterenol-Induced Heart Failure Rats. Chin. J. Integr. Med. 27, 424–431 (2021). https://doi.org/10.1007/s11655-020-2862-8
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DOI: https://doi.org/10.1007/s11655-020-2862-8