Effect of Gualou Xiebai Banxiatang on Mitochondrial Dysfunction and AMPK/PGC-1α Signaling Pathway in Rats with Ischemic Myocardial Injury
10.13422/j.cnki.syfjx.20221507
- VernacularTitle:瓜蒌薤白半夏汤对缺血性心肌损伤大鼠的线粒体功能障碍和AMPK/PGC-1α信号通路的影响
- Author:
Yingying TAN
1
;
Hui WANG
1
;
Yanbing WANG
1
;
Hong LI
1
;
Chengcheng MA
1
;
Qi ZHANG
1
Author Information
1. Basic Medical College，Shaanxi University of Chinese Medicine，Xiangyang 712046，China
- Publication Type:Journal Article
- Keywords:
Gualou Xiebai Banxiatang;
ischemic heart disease;
mitochondrial dysfunction;
adenosine 5’-monophosphate （AMP）-activated protein kinase （AMPK）;
peroxlsome proliferator-activated receptor-γ coactlvator-1α （PGC-1α）
- From:
Chinese Journal of Experimental Traditional Medical Formulae
2023;29(1):9-17
- CountryChina
- Language:Chinese
-
Abstract:
ObjectiveTo observe the effect of Gualou Xiebai Banxiatang on mitochondrial dysfunction and adenosine 5'-monophosphate （AMP）-activated protein kinase （AMPK）/peroxlsome proliferator-activated receptor-γ coactlvator-1α （PGC-1α） signaling pathway in rats with ischemic myocardial injury. MethodSeventy male SD rats were used in this experiment. Six rats from them were randomly selected as the control （CON） group， and the others were given high fat diet combined with isoproterenol injection （5 mg·kg-1·d-1， 7 d） to induce the rat model of ischemic heart disease based on hyperlipidemia. Successfully modeled rats were then randomly divided into model （MOD） group， high-dose Gualou Xiebai Banxiatang （GXBD-H） group， medium-dose Gualou Xiebai Banxiatang （GXBD-M） group， low-dose Gualou Xiebai Banxiatang （GXBD-L） group， and metoprolol （MET） group. Rats in the GXBD-H， GXBD-M， and GXBD-L groups were given 11.2， 5.6， 2.8 g·kg-1·d-1 Gualou Xiebai Banxiatang， those in the MET group were given 2.6 mg·kg-1·d-1 metoprolol， and those in the CON and MOD groups were given equal volume of pure water for 28 d. Hemodynamics were measured in rats by cardiac catheterization. Transmission electron microscopy was used to analyze myocardial mitochondria. Serum brain natriuretic peptide （BNP） and cardiac troponin T （cTnT） levels were detected by enzyme-linked immunosorbent assay （ELISA）. Mitochondrial membrane potential assay kit （JC-1 method） was applied for detecting mitochondrial membrane potential. The changes in the mitochondrial DNA copy number were measured by real-time quantitative polymerase chain reaction （Real-time PCR）. The content of adenosine triphosphate （ATP） in myocardial tissues was determined by spectrophotometer. The expression levels of p-AMPK， AMPK， PGC-1α， nuclear respiratory factor 1 （NRF1）， and mitochondrial transcription factor A （TFAM） in myocardium was detected by Western blot. ResultAs compared with the CON group， left ventricular end-systolic pressure （LVESP） and left ventricular end-diastole pressure （LVEDP） in the MOD group were significantly increased （P<0.05， P<0.01）， and +dp/dtmax and -dp/dtmax were significantly decreased （P<0.01）. In the MOD group， cardiac index and myocardial interstitial fibrosis area were significantly increased （P<0.01）， accompanied by mitochondrial damage， serum BNP， cTnT， and malondialdehyde （MDA） were significantly increased （P<0.01）， and serum superoxide dismutase （SOD） level was significantly decreased （P<0.01）. The myocardial mitochondrial membrane potential， DNA copy number， and ATP level were significantly decreased （P<0.01）， and the protein expression levels of p-AMPK/AMPK， PGC-1α， NRF1， and TFAM in myocardial tissues were significantly decreased in the MOD group （P<0.01）. Compared with the MOD group， the GXBD-H and GXBD-M groups significantly improved LVESP， LVEDP， +dp/dtmax， and -dp/dtmax （P<0.05， P<0.01）， significantly decreased heart index and myocardial interstitial fibrosis area （P<0.05， P<0.01）， and alleviated mitochondrial damage. In the GXBD-H and GXBD-M groups， serum BNP， cTnT， and MDA were decreased significantly （P<0.05， P<0.01）， serum SOD level was increased significantly （P<0.05）， and myocardial mitochondrial membrane potential， DNA copy number， and ATP level were significantly increased （P<0.05， P<0.01）. The protein levels of p-AMPK/AMPK， PGC-1α， NRF1， and TFAM in myocardial tissues were significantly increased in the GXBD-H and GXBD-M groups （P<0.05， P<0.01）. ConclusionGualou Xiebai Banxiatang has the effects of reducing the changes in cardiac function and myocardial pathology of rats with myocardial injury， inhibiting mitochondrial dysfunction， and up-regulating the protein expression levels of p-AMPK/AMPK， PGC-1α， NRF1， and TFAM in myocardial tissues. This study provides new laboratory evidence for in-depth exploration of the mechanism of this classical compound in preventing and treating myocardial injury.
