Effect of Linggui Zhugantang on Ventricular Remodeling After Myocardial Infarction and RhoA/ROCK Signaling Pathway
10.13422/j.cnki.syfjx.20250209
- VernacularTitle:苓桂术甘汤对心肌梗死后心室重构及RhoA/ROCK信号通路的影响
- Author:
Han REN
1
;
Wanzhu ZHAO
2
;
Shushu WANG
1
;
Rui CAI
2
;
Yuanhong ZHANG
2
;
Shengyi HUANG
1
;
Jinling HUANG
1
Author Information
1. School of Integrated Chinese Medicine and Western Medicine，Anhui University of Chinese Medicine，Hefei 230012，China
2. School of Chinese Medicine，Anhui University of Chinese Medicine， Hefei 230012，China
- Publication Type:Journal Article
- Keywords:
ventricular remodeling;
myocardial infarction;
Linggui Zhugantang;
Ras homologgene A （RhoA）/Rho-associated coiled-coil forming protein kinase （ROCK） signaling pathway;
myocardial fibrosis
- From:
Chinese Journal of Experimental Traditional Medical Formulae
2025;31(11):1-9
- CountryChina
- Language:Chinese
-
Abstract:
ObjectiveThis study aims to investigate the effects of Linggui Zhugantang （LGZGT） on ventricular remodeling （VR） in mice with myocardial infarction （MI） and its impact on the Ras homologgene A （RhoA）/Rho-associated coiled-coil forming protein kinase （ROCK） signaling pathway. MethodsThe MI model of mice was established by ligating the left anterior descending coronary artery （LAD）. They were divided into the sham-operated group， the model group， the low-dose， medium-dose， and high-dose groups of LGZGT （2.34， 4.68， 9.36 g·kg-1）， and the captopril group （3.25 mg·kg-1）， with 10 mice in each group. After four weeks of continuous drug administration by gavage， the level of cardiac function in each group of mice was examined using small animal Doppler ultrasound. Hematoxylin-eosin （HE） staining and Masson staining was used to assess the morphological changes of myocardial tissue and calculate the rate of collagen fiber deposition in mouse myocardial tissue. Wheat germ agglutinin （WGA） staining was employed to compare the cross-sectional area of cardiomyocytes in each group of mice. The expression levels of α-smooth muscle actin （α-SMA）， matrix metalloproteinase-2 （MMP-2）， type Ⅰcollagen （Col Ⅰ）， Col Ⅲ， tissue inhibitor of metalloproteinase 1（TIMP1）， B-cell lymphoma-2 （Bcl-2）-associated X protein （Bax）， Bcl-2， Caspase-3， and cleaved Caspase-3 were detected by Western blot. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was used to evaluate the mRNA levels of the pathway-related genes RhoA， ROCK1， and ROCK2. The protein expression levels of RhoA， ROCK1， and ROCK2 were tested by Western blot. ResultsThe level of cardiac function was markedly declined in the model group compared to the sham-operated group（P<0.01）. Myocardial tissue morphology changed significantly. The cross-sectional area of cardiomyocytes was significantly enlarged. The expression of α-SMA， MMP-2， Col Ⅰ， and Col Ⅲ was significantly upregulated（P<0.01）， and TIMP1 protein expression was significantly reduced（P<0.01）. The expressions of apoptosis-related proteins Bax were significantly up-regulated（P<0.01）， while the expression of Bcl-2 protein was significantly decreased（P<0.01）. The mRNA expression of RhoA， ROCK1， and ROCK2 were significantly upregulated （P<0.01）. Compared to the model group， the low-dose， medium-dose， and high-dose groups of LGZGT and the captopril group significantly reversed the experimental results of the model group in a dose-dependent manner （P<0.05， P<0.01）. ConclusionLGZGT significantly attenuated myocardial fibrosis， myocardial hypertrophy， and cardiomyocyte apoptosis after MI in mice and effectively reversed VR， the mechanism of which may be related to the modulation of the RhoA/ROCK signaling pathway.
