安体舒通对大鼠心肌梗死后心室重构和心肌间质胶原的影响  

Effects of High,Middle and Low-dose Spirolactone on the Prevention of Left Ventricular Remodeling and Collagen Accumulation After Acute Myocardial Infarction in Rats

作　　者：邱洪[1] 杨跃进[1] 田毅[2] 张沛[1] 阮英茆[3] 孙瑞成[4] 陈纪林[1] 高润霖[1] 陈在嘉[1] 

机构地区：[1]中国医学科学院中国协和医科大学心血管病研究所阜外心血管病医院冠心病诊治中心,北京市100037 [2]中国医学科学院中国协和医科大学心血管病研究所阜外心血管病医院实验外科,北京市100037 [3]中国医学科学院中国协和医科大学心血管病研究所阜外心血管病医院病理科,北京市100037 [4]中国医学科学院中国协和医科大学心血管病研究所阜外心血管病医院实验动物科,北京市100037

出　　处：《中国循环杂志》2003年第6期458-461,共4页Chinese Circulation Journal

摘　　要：目的 :观察醛固酮受体拮抗剂安体舒通对大鼠急性心肌梗死 (AMI)左心室重构和胶原增生的影响 ,探索醛固酮受体拮抗剂降低AMI后死亡率的机制。方法 :3 6只雌性Sprague Dawley (SD )AMI大鼠随机分为 :AMI对照组 (n =11)、安体舒通大剂量 [n =10 ,2 0mg/(kg·d) ]、中剂量 [n =8,10mg/(kg·d) ]和小剂量 [(n =7,5mg/(kg·d) ]组 ;另设假手术组 (n =8)。术后 4周行血流动力学测定、病理分析和非梗死区Ⅰ、Ⅲ型胶原含量的测定。结果 :AMI对照组与假手术组相比 ,左心室舒张末压、容积和重量均显著增加 (P <0 0 1～ 0 0 0 1) ;左心室球形指数、左心室内压最大上升和下降速率 (±dp/dt)及其校正值 (±dp/dt/LVSP)均显著降低 (P <0 0 1～ 0 0 0 1) ;左心室非梗死区Ⅰ、Ⅲ型胶原的含量均显著增加 (P均 <0 0 5 )。大、中、小剂量安体舒通组与AMI对照组相比 ,以上各指标多数无显著差异 (P >0 0 5 ) ,仅大剂量组左心室非梗死区Ⅰ、Ⅲ型胶原的含量均显著减少 (P均 <0 0 5 ) ,中剂量组仅Ⅲ型胶原含量显著减少 (P <0 0 5 )。结论 :大、中、小剂量安体舒通虽均不能显著改善大鼠AMI后左心室重构和左心室功能。但大剂量安体舒通能有效抑制AMI后左心室非梗死区Ⅰ、Ⅲ型胶原的增生 ,中剂量仅能抑制Ⅲ型胶原的增生。Objective: To evaluate the effects of high,middle and lowdose spirolactone on the prevention of left ventricular remodeling and collagen accumulation after acute myocardial infarction (AMI) in rats and to elucidate the mechanism of how the aldosterone antagonist reduces the mortality of AMI.Methods: Thirty-six AMI female SD rats were randomly assigned to AMI control ( n =11),highdose ( n =10,20 mg/( kg· d)),middledose (n =8,10 mg/( kg· d)) and lowdose spirolactone( n =7,5 mg/(kg·d))groups. Sham-operated rats( n =8) were selected randomly. After four weeks of therapy,hemodynamic studies,pathological analysis and collagen content studies were performed.Results: Compared with sham-operated group,left ventricular (LV) end diastolic pressures,LV end diastolic volume and LV absolute weight were significantly increased ( p <0.01-0.001),left ventricular sphericity index and LV pressure maximal rates of rise and fall(±dp/dt) as well as their corrected values (±dp/dt/LVSP) were all significantly reduced ( p < 0.01- 0.001),and type Ⅰ and Ⅲ collagen contents were significantly increased in the noninfarcted LV myocardium( p <0.05)in the AMI control group. Compared with AMI group,all indicators as stated above,did not change significantly( p >0.05),except that both type Ⅰ and type Ⅲ collagen contents in the noninfarcted LV myocardium were significantly reduced in the highdose group( p <0.05). Middledose spirolactoned significantly decrease only type Ⅲ collagen content in the noninfarcted LV myocardium. Conclusion: The high,middle and lowdose spirolactone can't effectively prevent LV remodeling nor improve LV function,though the highdose spirolactone can significantly reduce type Ⅰ and type Ⅲ collagen contents in the noninfarcted LV myocardium( p <0.05). The middledose spirolactone can significantly decrease only type Ⅲ collagen content in the noninfarcted LV myocardium.

关 键 词：安体舒通 大鼠 心肌梗死 心室重构 胶原 醛固酮受体拮抗剂 

分 类 号：R542.22[医药卫生—心血管疾病] R972[医药卫生—内科学]