低剂量福辛普利与厄贝沙坦联合应用对大鼠实验性心肌梗死的保护作用及其机制

Protective effects of fosinopril and erbasartan with low doses on acute myocardial infarction in rats and mechanism

目的:观察低剂量福辛普利与厄贝沙坦联合应用对大鼠实验性心肌梗死的保护作用,阐明其保护作用的机制。方法:Wistar大鼠随机分为假手术组、模型组、福辛普利(20mg.kg-1)组、厄贝沙坦(100mg.kg-1)组及福辛普利+厄贝沙坦(10mg.kg-1+50mg.kg-1)组,每组10只,除假手术组外其余各组结扎大鼠左冠状动脉前降支建立急性心肌梗死模型,测定大鼠心肌梗死面积(MIS)、血清肌酸磷酸激酶(CK)、乳酸脱氢酶(LDH)和天门冬氨酸氨基转换酶(AST)活性,血浆内皮素(ET)和血管紧张素Ⅱ(AngⅡ)含量、心肌缺血区和非缺血区游离脂肪酸(FFA)水平以及全血和血浆黏度等指标,并与单纯应用福辛普利(20mg.kg-1)组和厄贝沙坦(100mg.kg-1)组进行比较。结果:与模型组比较,假手术组、福辛普利与厄贝沙坦减半剂量联合应用组、单纯应用福辛普利或厄贝沙坦全剂量组急性心肌梗死大鼠的MIS明显缩小(P<0.05或P<0.01),血清CK、LDH和AST活性明显降低(P<0.05或P<0.01),血浆ET含量及心肌缺血区FFA水平明显降低(P<0.05),全血低、中、高切黏度和血浆黏度明显降低(P<0.05),血浆AngⅡ含量及心肌非缺血区FFA水平无明显变化。结论:低剂量福辛普利与厄贝沙坦联合应用对大鼠急性心肌梗死具有明显保护作用,与单纯应用高剂量福辛普利或厄贝沙坦的作用效果相当,其作用机制可能与减轻FFA及ET对心肌的损害、改善心肌代谢、纠正心肌缺血时血流状态及防止血栓形成等作用有关。

Objective To observe the the protective effect of combination of low dose fosinopril and erbasartan on experimental myocardial infarction in rats and its mechanism. Methods Wistar rats were randomly divided into sham operation, model, fosinopril （20 mg·kg^-1）, erbasartan （100 mg·kg^-1） and fosinopril ＋ erbasartan （10 mg·kg^-1＋50 mg·kg^-1） groups. The acute myocardial infarction models were established with ligation of left anterior descending coronary artery in rats except sham operation group. The effects of fosinopril and erbasartan and combination of fosinopril and erbasartan on myocardial infarct size （MIS） and the activities of serum creatine phosphokinase （CK）, lactate dehydrogenase （LDH） and aspartate aminotransferase （AST）, the contents of plasma endothelin （ET） and angiotensinⅡ （Ang Ⅱ）, the level of myocardial free fatty acid （FFA） in ischemic and non-ischemic area, and the viscosities of blood and plasma were determined. Results Compared with model group, the MIS in sham operation, fosinopril, erbasartan and fosinopril ＋ erbasartan groups was significantly reduced （P〈0.05 or P〈0.01）, the activities of serum CK, LDH and AST were significantly decreased （P〈0.05 or P〈 0.01）, the contents of plasma ET and the levels of myocardial FFA in ischemic area were significantly decreased （P〈0.05）, and the viscosities of blood and plasma were also significantly decreased （P〈0.05）, but the contents of plasma AngⅡ and the levels of myocardial FFA in non ischemic area had no significant changes. Conclusion Low dose fosinopril combined with erbasartan has protective effect on acute myocardial infarction in rats, just as high dose fosinopril or erbasartan, by reducing damage of FFA and ET on myocardium, improving myocardial metabolism, correcting state of bloodstream in myocardial isehemia and preventing thrombosis etc.