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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 protective effect of low-dose fosinopril combined with irbesartan on experimental myocardial infarction in rats and to elucidate the mechanism of its protective effect. Methods: Wistar rats were randomly divided into sham operation group, model group, fosinopril (20mg.kg-1) group, irbesartan (100mg.kg-1) group and fosinopril + irbesartan (10mg.kg-1 +50 mg.kg-1), 10 rats in each group. Except the sham-operation group, the rats in each group were ligated to establish the model of acute myocardial infarction by ligating the anterior descending branch of left anterior descending coronary artery. The area of myocardial infarction MIS, serum creatine phosphokinase, lactate dehydrogenase (LDH) and aspartate aminotransferase (AST), plasma endothelin (ET) and angiotensin Ⅱ (AngⅡ) Free fatty acid (FFA) in blood and non-ischemic area, and the indexes of whole blood and plasma viscosity were compared with those of pure group (20mg.kg-1) and irbesartan (100mg.kg-1) Group to compare. Results: Compared with the model group, the MIS of sham-operated group, fosinopril and irbesartan reduced by half dose, the application of fosinopril or irbesartan full-dose group of acute myocardial infarction rats significantly reduced MIS (P <0.05 or P <0.01), serum CK, LDH and AST decreased significantly (P <0.05 or P <0.01), plasma ET content and FFA level in myocardial ischemic area decreased significantly , Middle and high shear viscosity and plasma viscosity (P <0.05), plasma Ang Ⅱ content and myocardial non-ischemic FFA levels did not change significantly. Conclusion: The combination of low-dose fosinopril and irbesartan has a significant protective effect on acute myocardial infarction in rats, which is equivalent to the simple application of high-dose fosinopril or irbesartan. The mechanism of action may be related to Reduce the damage of FFA and ET on myocardial, improve myocardial metabolism, correct the state of blood flow during myocardial ischemia and prevent thrombosis.