Linggui Zhugan Decoction (苓桂术甘汤) Inhibits Ventricular Remodeling after Acute Myocardial Infarction in Rats by Suppressing TGF-β<sub>1</sub>/Smad Signaling Pathway

Liang WANG; Hui SHI; Jin-ling HUANG; Shan XU; Pei-pei LIU

doi:10.1007/s11655-018-3024-0

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Linggui Zhugan Decoction (苓桂术甘汤) Inhibits Ventricular Remodeling after Acute Myocardial Infarction in Rats by Suppressing TGF-β₁/Smad Signaling Pathway

Original Article | Updated：2021-08-23

- Linggui Zhugan Decoction (苓桂术甘汤) Inhibits Ventricular Remodeling after Acute Myocardial Infarction in Rats by Suppressing TGF-β₁/Smad Signaling Pathway
- Linggui Zhugan Decoction (苓桂术甘汤) Inhibits Ventricular Remodeling after Acute Myocardial Infarction in Rats by Suppressing TGF-β₁/Smad Signaling Pathway
- Chinese Journal of Integrative Medicine 2020年26卷第5期页码：345-352
- Affiliations：
  
  1.College of Integrated Chinese and Western Medicine, Anhui University of Chinese Medicine, Hefei (230012), China
  2.Anhui Province Key Laboratory of Chinese Medicinal Formula, Hefei (230012), China
  3.Graduate School, Anhui University of Chinese Medicine, Hefei (230012), China
- Author bio：
  
  Correspondence to: Prof. HUANG Jin-ling, E-mail:jinling6181@126.com
- Funds：
  
  the National Natural Science Foundatio of China(30973707;81373533;81202631);the Natural Science Foundation of Anhui Province(1508085QH192;1608085QH222)
- DOI：10.1007/s11655-018-3024-0
  中图分类号：
- 纸质出版日期：2020-05-01，
  
  网络出版日期：2019-01-09，
  
  录用日期：2018-05-30
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Liang WANG, Hui SHI, Jin-ling HUANG, 等. Linggui Zhugan Decoction (苓桂术甘汤) Inhibits Ventricular Remodeling after Acute Myocardial Infarction in Rats by Suppressing TGF-β₁/Smad Signaling Pathway[J]. Chinese Journal of Integrative Medicine, 2020,26(5):345-352.

Liang WANG, Hui SHI, Jin-ling HUANG, et al. Linggui Zhugan Decoction (苓桂术甘汤) Inhibits Ventricular Remodeling after Acute Myocardial Infarction in Rats by Suppressing TGF-β₁/Smad Signaling Pathway[J]. Chinese Journal of Integrative Medicine, 2020,26(5):345-352.
Liang WANG, Hui SHI, Jin-ling HUANG, 等. Linggui Zhugan Decoction (苓桂术甘汤) Inhibits Ventricular Remodeling after Acute Myocardial Infarction in Rats by Suppressing TGF-β₁/Smad Signaling Pathway[J]. Chinese Journal of Integrative Medicine, 2020,26(5):345-352. DOI： 10.1007/s11655-018-3024-0.

Liang WANG, Hui SHI, Jin-ling HUANG, et al. Linggui Zhugan Decoction (苓桂术甘汤) Inhibits Ventricular Remodeling after Acute Myocardial Infarction in Rats by Suppressing TGF-β₁/Smad Signaling Pathway[J]. Chinese Journal of Integrative Medicine, 2020,26(5):345-352. DOI： 10.1007/s11655-018-3024-0.

摘要

Abstract

Objective:

To investigate the inhibitory effect of Linggui Zhugan Decoction (LZD

苓桂术甘汤) on the ventricular remodeling (VR) after acute myocardial infarction (AMI) and related mRNA and proteins expression in transforming growth factor-beta 1 (TGF-β

)/Smad signaling pathway

and explain its putative mechanism.

Methods:

A VR model was generated by ligation of coronary artery in rats. Two weeks after surgery

60 rats were randomly divided into the model group

the sham-operation group (distilled water)

the positive control group (2.4 mg/kg simvastatin)

and the low-

medium- and high-dose LZD groups (2.1

4.2

8.4 g crude drug/kg

respectively) by a random number table

10 rats in each group. Rats in each group was treated for 4 weeks. Changes of hemodynamics indices and cardiac weight index were detected by the PowerLab data acquisition and analysis recording instrument. Morphology changes of myocardial tissue were observed by hematoxylin-eosin and Masson staining. The expressions of TGF-β

Smad2

Smad3

p-Smad2 and p-Smad3 in myocardial tissue were detected by Western blotting. The mRNA expressions of TGF-β1

Smad2 and Smad3 were detected by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). The expressions of matrix metalloprotein 2 (MMP2)

MMP9

collagen Ⅰ and collagen Ⅲ were observed by immunohistochemical methods.

Results:

VR rats showed significant dysfunction in hemodynamic indices and cardiac structure and function. Compared with the shamoperation group

myocardial tissue damage

interstitial fibrosis occurred in the model rats

left ventricular systolic pressure (LVSP)

left ventricular pressure maximum contraction rate (+dp/dt

max

) and left ventricular pressure maximum relaxation rate (-dp/dt

max

) decreased significantly (all

0.01)

while left ventricular end-diastolic pressure (LVEDP)

cardiac weight index and left ventricular weight index elevated significantly

meanwhile TGF-β

p-Smad2

p-Smad3

Smad2

Smad3

MMP2

MMP9

collagen Ⅰ

collagen Ⅲ protein expressions in myocardial tissue and TGF-β

Smad2 and Smad3 mRNA expressions increased significantly (all

0.01). Compared with the model group

LZD could significantly improve the pathological changes of myocardial tissue

increase LVSP

+dp/dtmax and -dp/dt

max

lower LVEDP

reduce the whole heart weight index and left ventricular weight index and inhibit the over-expressions of TGF-β

p-Smad2

p-Smad3

Smad2

Smad3

MMP2

MMP9

collagen Ⅰ and collagen Ⅲ proteins in myocardial tissue and mRNA expressions of TGF-β

Smad2 and Smad3 (

0.05 or

0.01).

Conclusion:

LZD can significantly suppress VR induced by AMI

and its underlying mechanism may be associated with its inhibitory effect on the TGF-β

/Smad signaling pathway.

关键词

Keywords

Linggui Zhugan Decoctionacute myocardial infarctionventricular remodelingtransforming growth factor-beta 1/Smad signaling pathwayChinese medicine

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Linggui Zhugan Decoction (苓桂术甘汤) Inhibits Ventricular Remodeling after Acute Myocardial Infarction in Rats by Suppressing TGF-β1/Smad Signaling Pathway

Linggui Zhugan Decoction (苓桂术甘汤) Inhibits Ventricular Remodeling after Acute Myocardial Infarction in Rats by Suppressing TGF-β1/Smad Signaling Pathway

DOI：10.1007/s11655-018-3024-0

摘要

Abstract

关键词

Keywords

references

Linggui Zhugan Decoction (苓桂术甘汤) Inhibits Ventricular Remodeling after Acute Myocardial Infarction in Rats by Suppressing TGF-β₁/Smad Signaling Pathway

Linggui Zhugan Decoction (苓桂术甘汤) Inhibits Ventricular Remodeling after Acute Myocardial Infarction in Rats by Suppressing TGF-β₁/Smad Signaling Pathway