关键词: 黄芪甲甙, 急性心肌梗死, 心室重构, NOX/ROS/TNF-α信号通路

Abstract:

The aim of this study was to explore the role and mechanism of Astragaloside Ⅳ on ventricular remodeling in rats with acute myocardial infarction. 36 Wistar rats were selected and randomly divided into sham operation group， model group， low-dose Astragaloside Ⅳ group， middle-dose Astragaloside Ⅳ group， high-dose Astragaloside Ⅳ group and positive control group， with 6 rats in each group. Except for the sham operation group， the remaining rats were operated to establish rat models of acute myocardial infarction. Rats in the sham operation group were only separated from the left anterior descending coronary artery after thoracotomy and then sutured layer by layer without ligation， and received drug intervention on the 2^nd day after modeling. The low-dose， middle-dose and high-dose Astragaloside Ⅳ groups were given Astragaloside Ⅳ by gavage at the doses of 20， 40 and 60 mg·kg^-1 respectively， and the positive control group was given 100 mg·kg^-1 of aspirin by gavage. The cardiac function indicators ［left ventricular ejection fraction （LVEF）， left ventricular fractional shortening （LVFS）， left ventricular mass index （LVMI）］ were compared among the groups on the 0^th， 2^nd and 4^th week of treatment. Cardiac hemodynamic monitoring system was applied to detect the cardiac hemodynamic indicators ［left ventricular end diastolic pressure （LVEDP）， left ventricular systolic pressure （LVSP）， maximum rise rate of left ventricular pressure increase/decrease （±dp/dt_max）］. The levels of serum angiotensin Ⅱ （Ang Ⅱ）， endothelin 1 （ET-1） and brain natriuretic peptide （BNP） were measured by enzyme-linked immunosorbent assay. Kit was used for detection of myocardial tissue reactive oxygen species （ROS） content， and real-time fluorescence quantitative PCR and Western blot were adopted to detect the mRNA relative expression levels and protein expression levels of NADPH oxidase （reduced nicotinamide adenine dinucleotide phosphate oxidase， NOX） and tumor necrosis factor α （TNF-α） in myocardial tissues of rats. Results showed that， after 4 weeks of treatment， the LVEF and LVFS were increased with treatment time in the high-dose Astragaloside Ⅳ group and positive control group （P<0.05）. Compared to the sham operation group at the same time of treatment， the LVEF and LVFS of the model group were significantly decreased （P<0.05）. There were no statistically difference in LVEF and LVFS in each treatment group compared to the model group on the 0^th week of treatment （P>0.05）. The LVEF and LVFS were obviously enhanced in the middle-dose Astragaloside Ⅳ group， high-dose Astragaloside Ⅳ group and positive control group compared to the model group on the 2^nd and 4^th week （P<0.05）. Compared with the model group， the LVMI of middle-dose Astragaloside Ⅳ group， high-dose Astragaloside Ⅳ group and positive control group were significantly decreased （P<0.05） while the LVSP， LVEDP and ±dp/dt were risen significantly （P<0.05）， and the levels of serum Ang Ⅱ， ET-1 and BNP were obviously reduced （P<0.05）， and the myocardial tissue ROS content was significantly lowered （P<0.05）， and gene and protein expression levels of NOX and TNF-α were significantly decreased. The result of study showed that Astragaloside Ⅳ can improve the cardiac function and hemodynamic disorders and inhibit the ventricular remodeling of rats with AMI， which may be related to the down-regulations of expressions of NOX/ROS/TNF-α signaling pathways.

Key words: astragaloside Ⅳ, acute myocardial infarction, ventricular remodeling, NOX/ROS/TNF-α signaling pathways