Effects of Tingli dazao xiefei decoction on ventricular remodeling in model rats with heart failure after myocardial infarction through ACE2-Ang（-1-7）-Mas axis
- VernacularTitle:葶苈大枣泻肺汤通过ACE2-Ang（-1-7）-Mas轴对心梗后心衰模型大鼠心室重构的影响
- Author:
Zhongjie YUAN
1
;
Xuanxuan HAO
2
;
Bin LI
3
;
Shiyang XIE
3
;
Xinlu WANG
3
;
Youping WANG
3
;
Xindi CHANG
1
;
Yu BAO
1
;
Mingjun ZHU
3
Author Information
1. The First Clinical Medical College，Henan University of Chinese Medicine，Zhengzhou 450099，China
2. Dept. of Cardiology，the First Affiliated Hospital，Guizhou University of Chinese Medicine，Guizhou 550001，China
3. Heart Center，the First Affiliated Hospital，Henan University of Chinese Medicine，Zhengzhou 450099，China
- Publication Type:Journal Article
- Keywords:
Tingli dazao xiefei decoction;
heart failure;
ventricular remodeling;
ACE2-Ang（- 1-7）-Mas axis
- From:
China Pharmacy
2023;34(2):161-167
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE To explore the mechanism of Tingli dazao xiefei decoction on ventricular remodeling in model rats with heart failure after myocardial infarction. METHODS The rat model of heart failure after myocardial infarction was established by ligation of anterior descending branch of left coronary artery， which was divided into 8 groups： sham operation group， model group， A779 group （1 mg/kg）， A779 （1 mg/kg）+Tingli dazao xiefei decoction equivalent-dose group （0.8 g/kg）， A779 （1 mg/kg） +Tingli dazao xiefei decoction high-dose group （1.6 g/kg）， Tingli dazao xiefei decoction equivalent-dose group （0.8 g/kg）， Tingli dazao xiefei decoction high-dose group （1.6 g/kg） and losartan potassium group （10 mg/kg）. Each group was given equal volume of distilled water or corresponding drugs intragastrically for 4 weeks. Masson staining was used to determine the distribution of collagen fibers in rat myocardium. The content of hydroxyproline （Hyp） in myocardium was determined by alkaline hydrolyzation. The expressions of type Ⅰ and Ⅲ collagen （COLⅠ， COLⅢ）in myocardium were detected by immunohisto-chemistry. Myocardial fibrosis-related indexes such as matrix metalloproteinase-2 （MMP-2）， MMP-9， tissue inhibitor of metalloproteinase-1 （TIMP-1） and soluble suppression of tumorigenicity-2 （sST-2） were detected by ELISA. The protein expressions of angiotensin converting enzyme 2-angiotensin-（1-7）-Mas [ACE2-Ang-（1-7）-Mas] axis were detected by Western blot. RESULTS Compared with sham operation group， myocardial cells in model group and A779 group were disordered， collagen fiber deposition was significantly increased and myocardial fibrosis was obvious； the Hyp content and MMP-2， MMP-9， sST-2 levels were increased， and COL Ⅰ and COL Ⅲ positive expressions were significantly enhanced； TIMP-1 level， protein expressions of ACE2， Ang-（1-7） and Mas were significantly decreased （P＜0.05）. Compared with model group， above indexes of Tingli dazao xiefei decoction equivalent-dose and high-dose groups were improved to different extents. Compared with A779 group， A779+Tingli dazao xiefei decoction equivalent-dose and A779+high-dose groups could improve myocardial arrangement and collagen distribution， reduce the Hyp content and MMP-2， MMP-9 levels， reduce positive expressions of COL Ⅰ and COL Ⅲ （P＜0.05）， but couldn’t improve Ang-（1-7） and Mas protein expression. CONCLUSIONS Tingli dazao xiefei decoction can improve ventricular remodeling in myocardial failure model rats after myocardial infarction by improving the expression of ACE2- Ang（- 1-7）-Mas axis proteins.
