摘要
背景:心肌纤维化是心脏基质成分合成与降解代谢失平衡的结果,是受损心肌组织僵硬度的结构基础,中药黄芪具有强心、利尿等作用,但对心肌胶原的影响尚需实践中认识。目的:观察黄芪皂甙IV对急性心肌梗死模型大鼠心肌胶原及心功能的影响,探讨该影响与黄芪皂甙IV的量效与时效关系。设计:完全随机分组设计,随机对照实验。单位:青岛大学医学院附属医院儿科。材料:实验于2003-07/2004-02在青岛大学医学院脑病研究所完成。实验选用132只清洁级Wistar大鼠,随机将大鼠分为3组,分别为对照组11只、缺血组10只、黄芪皂甙IV组121只。方法:对照组只开胸而不结扎左冠状动脉前降支;缺血组开胸结扎左冠状动脉前降支,造成大鼠急性心肌梗死模型;黄芪皂甙IV组造模成功后给予黄芪皂甙IV。测定大鼠血流动力学指标、心功能和心肌胶原的变化,观察黄芪皂甙IV对缺血大鼠心肌胶原和心功能的量-效和时-效关系。主要观察指标:①黄芪皂甙IV对心肌梗死大鼠左心室心肌胶原含量的影响及其量效和时效关系。②黄芪皂甙IV对大鼠心功能和血流动力学的影响及其量效和时效关系。结果:按实际处理分析,进入结果分析100只大鼠。对照组10只,缺血组10只,黄芪皂甙IV组80只。黄芪皂甙IV5个剂量组[2.5,5.0,10.0,15.0,20.0mg/(kg·d)]及术后5个时间点(3,7,14,21,28d)各8只。由于黄芪皂甙IV对缺血心肌的作用在15.0mg/(kg·d)时最明显,故选择这一剂量做时效关系的观察。①左室梗死区心肌组织内胶原的含量、血清羧基末端前胶原I型多肽和氨基末端前胶原III型多肽浓度:给予黄芪皂甙IV后,随着黄芪皂甙IV剂量的增加和黄芪皂甙IV[15.0mg/(kg·d)]作用时间的延长而逐渐下降(P<0.05～0.01);血清羧基末端前胶原I型多肽和氨基末端前胶原III型多肽浓度:在黄芪皂甙IV剂量为10mg/kg和黄芪皂甙IV应用21d时恢复到对照组水平;心肌组织内胶原的含量:左室梗死区较左室非梗死区高(P<0.01),右室和左室非梗死区在应用黄芪皂甙IV前后无明显变化。②缺血大鼠心功能:给予黄芪皂甙IV后明显改善(P<0.05～0.01),随着黄芪皂甙IV剂量的增加和黄芪皂甙IV作用时间的延长,缺血大鼠的心输出量、心率、左室每博输出量、平均动脉压、动脉收缩压,左室搏出功逐渐恢复到对照组水平。结论:黄芪皂甙IV可抑制心肌梗死大鼠心肌胶原的增生,改善大鼠心功能,且胶原含量随黄芪皂甙IV剂量增大及作用时间延长而下降,心功能随着黄芪皂甙IV剂量增大和作用时间延长而改善。
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 Ⅲpropeptide 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 I propeptide and aminoterminal procollagen type Ⅲ propeptide returned to the level of control at a dose of 10 mg·kg-1 per 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.
出处
《中国临床康复》
CSCD
北大核心
2005年第23期207-209,共3页
Chinese Journal of Clinical Rehabilitation
基金
青岛市自然科学基金资助(04-2-JZ-97)~~
