Dosage and time effects of astragaloside Ⅳ on myocardial collagen and cardiac function of ischemic rats
- VernacularTitle:缺血大鼠心肌胶原和心功能改变与黄芪皂甙Ⅳ的量效和时效关系
- Author:
Zipu LI
;
Qian CAO
;
Xiuying PANG
- Publication Type:Journal Article
- From:
Chinese Journal of Tissue Engineering Research
2005;9(23):207-209
- CountryChina
- Language:Chinese
-
Abstract:
BACKGROUND: Cardiac fibrosis, which results from the loss of balance between synthesis and degradation of cardiac matrix component, is the structural foundation of the stiffness of damaged myocardial tissues. Astragalus membranaceus, a traditional Chinese herb, has multiple functions such as exerting a tonic effect on the heart to induce diuresis. However,the effect of astragaloside Ⅳ on cardiac collagen is poorly known in practice.OBJECTIVE: To observe the effects of astragaloside Ⅳ on myocardial collagen and cardiac function in ischemic rats and to investigate the dosage and time effects of astragaloside Ⅳ.DESIGN: A completely randomized grouping design and randomized controlled trial.SETTING: Department of Pediatrics, the Affiliated Hospital of Medical College of Qingdao University.MATERIALS: The study was conducted in the Encephalopathy Research Institute, Medical College of Qingdao University, from July 2003 to February 2004. Totally 132 Wistar rats of cleaning grade were randomized into three groups: control group (n=11), ischemic group (n=10) and astragaloside Ⅳ group (n=121).METHODS: Rats in control group had thoracotomy, but did not have their left anterior descending coronary artery ligated; rats in ischemic group had thoracotomy and had their left anterior descending coronary artery ligated to establish acute myocardial infarction model; rats in astragaloside Ⅳ group were given astragaloside Ⅳ after surgical ligature of left anterior descending coronary artery. The changes in hemodynamic parameters, cardiac function and myocardial collagen were determined. The dosage and time effects of astragaloside Ⅳ on myocardial collagen and cardiac function were observed.MAIN OUTCOME MEASURES: ① The dosage and time effect of astragaloside Ⅳ on the content of myocardial collagen in the left ventricle of rats with myocardial infarction; ② The dosage and time effects of astragaloside Ⅳ on hemodynamics and cardiac function of rats with myocardial infarction.RESULTS: One hundred rats entered the results analysis. There were 10 in control group and ischemic group, respectively, and 80 in astragaloside Ⅳ group. The five dosage groups of astragaloside Ⅳ [2.5, 5.0, 10.0, 15.0 and 20.0 mg/(kg·d)] and the five postoperative time points (3, 7, 14, 21 and 28 days) had eight rats for each. Astragaloside Ⅳ at a dose of 15.0 mg/kg per day was found to have the most marked effect on ischemic myocardium, so this dose was chosen for observing time effect. ① After administration of astragaloside Ⅳ, the content of collagen in myocardial tissues of the infarcted area of left ventricle, the serum concentration of carboxyterminal procollagen type Ⅰ propeptide and aminoterminal procollagen type Ⅲ propeptide decreased gradually with the increased dose of astragaloside Ⅳ and with the prolonged action time of astragaloside Ⅳ [15 mg/(kg·d)] (P ＜ 0.05-0.01). The serum concentration of carboxyterminal procollagen type 1 propeptide and aminoterminal procollagen type Ⅲ propeptide returned to the level of control at a dose of 10 mg·kg-1per day and at 21 days after astragaloside Ⅳ administration, respectively. The content of collagen in myocardial tissues of the infarcted area of left ventricle was higher than that of non-infarcted area (P＜ 0.01); there were no significant changes in the content of cardiac collagen of right ventricle and non-infarcted area of left ventricle before and after astragaloside Ⅳ administration. ② The cardiac function of ischemic rats significantly improved after astragaloside Ⅳ administration (P ＜ 0.05-0.01); cardiac output, heart rate, stroke volume,mean aortic pressure, systolic aortic pressure, and the stroke work of left ventricle gradually returned to the level of control with the increased dose of astragaloside Ⅳ and with the prolonged action time of astragaloside Ⅳ.CONCLUSION: Astragaloside Ⅳ can inhibit the proliferation of cardiac collagen and improve cardiac function in rats with myocardial infarction.The content of myocardial collagen gradually decreases and cardiac function gradually improves with the increased dose of astragaloside Ⅳ and the prolonged action time of astragaloside Ⅳ.
