Huoxin Pill (活心丸) Attenuates Cardiac Fibrosis by Suppressing TGF-β1/Smad2/3 Pathway in Isoproterenol-Induced Heart Failure Rats

Mei-zhong PENG; Mei-ling YANG; A-ling SHEN; Xue-ling ZHOU; Yan LU; Qi LI; Zhi-qing SHEN; Bin HUANG; Jun PENG; Jian-feng CHU

doi:10.1007/s11655-020-2862-8

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Huoxin Pill (活心丸) Attenuates Cardiac Fibrosis by Suppressing TGF-β1/Smad2/3 Pathway in Isoproterenol-Induced Heart Failure Rats

Original Article | Updated：2021-09-01

- Huoxin Pill (活心丸) Attenuates Cardiac Fibrosis by Suppressing TGF-β1/Smad2/3 Pathway in Isoproterenol-Induced Heart Failure Rats
- Huoxin Pill (活心丸) Attenuates Cardiac Fibrosis by Suppressing TGF-β1/Smad2/3 Pathway in Isoproterenol-Induced Heart Failure Rats
- Chinese Journal of Integrative Medicine 2021年27卷第6期页码：424-431
- Affiliations：
  
  1.Academy of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou (350122), China
  2.Chen Keji Academic Thought Inheritance Studio, Fujian University of Traditional Chinese Medicine, Fuzhou (350122), China
  3.Fujian Key Laboratory of Integrative Medicine on Geriatrics, Fujian University of Traditional Chinese Medicine, Fuzhou (350122), China
  4.The Third People's Hospital Affiliated to Fujian University of Traditional Chinese Medicine, Fuzhou (350122), China
  5.Department of Research and Development, Youcare Pharmaceutical Group Co., Ltd., Beijing (100176), China
- Author bio：
  
  Dr. CHU Jian-feng, E-mail: jianfengchu@126.com
- Funds：
  
  the National Natural Science Foundation of China(81774135;81302884);Science and Technology Major Project of Fujian Province(2019YZ014004);Natural Science Foundations of Fujian Province(2018J01884);Fujian Provincial Health and Family Planning Commission(2018-CX-42)
- DOI：10.1007/s11655-020-2862-8
  中图分类号：
- 纸质出版日期：2021-06-01，
  
  网络出版日期：2020-12-22，
  
  录用日期：2020-06-16
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Mei-zhong PENG, Mei-ling YANG, A-ling SHEN, 等. Huoxin Pill (活心丸) Attenuates Cardiac Fibrosis by Suppressing TGF-β1/Smad2/3 Pathway in Isoproterenol-Induced Heart Failure Rats[J]. Chinese Journal of Integrative Medicine, 2021,27(6):424-431.

Mei-zhong PENG, Mei-ling YANG, A-ling SHEN, et al. Huoxin Pill (活心丸) Attenuates Cardiac Fibrosis by Suppressing TGF-β1/Smad2/3 Pathway in Isoproterenol-Induced Heart Failure Rats[J]. Chinese Journal of Integrative Medicine, 2021,27(6):424-431.
Mei-zhong PENG, Mei-ling YANG, A-ling SHEN, 等. Huoxin Pill (活心丸) Attenuates Cardiac Fibrosis by Suppressing TGF-β1/Smad2/3 Pathway in Isoproterenol-Induced Heart Failure Rats[J]. Chinese Journal of Integrative Medicine, 2021,27(6):424-431. DOI： 10.1007/s11655-020-2862-8.

Mei-zhong PENG, Mei-ling YANG, A-ling SHEN, et al. Huoxin Pill (活心丸) Attenuates Cardiac Fibrosis by Suppressing TGF-β1/Smad2/3 Pathway in Isoproterenol-Induced Heart Failure Rats[J]. Chinese Journal of Integrative Medicine, 2021,27(6):424-431. DOI： 10.1007/s11655-020-2862-8.

摘要

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

isosorbide mononitrate (ISMN)

HXP low (HXP-L)

and HXP high (HXP-H) groups (

=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-β1 (TGF-β1)/Smads pathway was further explored using immunohistochemistry (IHC) and Westernblot 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 (

0.05). Moreover

HXP treatment obviously attenuated the increase of HWI and serum level of creatine kinase MB (CK-MB

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-β1 and p-Smad2/3 protein expression in cardiac tissues of HF rats (

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-β1/Smad2/3 pathway.

关键词

Keywords

Huoxin Pillheart failurecardiac fibrosisisoproterenolTGF-β1/Smad2/3 pathway

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