西拉普利和阿司匹林对实验性大鼠心肌梗死后心脏间质胶原代谢的影响

Effect of cilazapril and aspirin on the myocardial collagen after myocardial infarction in rats

目的:观察西拉普利和阿司匹林对实验性大鼠心肌梗死(MI)后心脏间质胶原代谢的影响。方法:采用结扎冠状动脉(冠脉)左前降支的方法建立大鼠MI模型,设立假手术组、梗死组、西拉普利组、阿司匹林组、联合组。术后2周测定循环中血管紧张素Ⅱ(AngⅡ)、6酮PGF1α(6ketoPGF1α)、内皮素1(ET1)水平和心脏梗死区、左室非梗死区及右室的间质胶原含量。结果:各实验组与假手术组比较,血循环中AngⅡ、ET1升高,6ketoPGF1α降低,左室非梗死区及右室的胶原含量明显升高。各实验组间梗死区的胶原含量相互比较差异无统计学意义。与梗死组比较,阿司匹林组血6ketoPGF1α显著降低,左室非梗死区及右室的胶原含量差异无统计学意义;西拉普利组、联合组血AngⅡ、ET1明显降低,6ketoPGF1α显著升高,左室非梗死区及右室的胶原含量明显降低。联合组与西拉普利组比较,6ketoPGF1α显著降低,而左室非梗死区及右室的胶原含量差异无统计学意义。结论:MI后神经内分泌系统过度激活,循环中AngⅡ、ET1明显升高并导致心脏间质胶原含量的升高。西拉普利通过抑制循环紧素血管紧张素醛固酮系统和内皮素系统,降低AngⅡ和ET1,并通过抑制缓激肽降解,抑制心脏非梗死区间质胶原的过度沉积。阿司匹林对MI后心脏间质胶原的沉积无明显影响。西拉普利与阿司匹林联合应用不影响西拉普利的抑制非梗死区心脏间质胶原过度沉积的作用。

Object：The study is to compare the effects of cilazapril alone, Aspirin alone, and combination of cilazapril and Aspirin on myocardial collagen in a model of MI of rats. Method： Myocardial infarction was induced in 56 Wistar male rats by ligation of the anterior descending coronary artery. Sham-operated rats served as controls. One day （A group） after the operation, rats were randomized into 4 groups： C group （Cilazapril）, D group （Aspirin） , E group （Cilazapril and Aspirin ）, the rats who did not receive any drug treatment were in B group. After two weeks, all the rats were sacrificed. The levels of plasma angiotension Ⅱ, 6-keto-PGF1aand endothelin were measured. The myocardial collagen contents （hydroxyproline levels） including infarct area, noninfarct area of left ventricular and right ventricular were assessed. Result：The myocardial collagen contents in noninfarct area of left ventricular and right ventricular were strikingly higher in four operated groups than Sham-operated group. There was no significant difference in the content of infarct area among the four operated groups. The contents in noninfarct area of left ventricular and right ventricular were reduced in C and E group compared with B group. There was no significant difference in the myocardial collagen content between C and E group, similarly between B and D group. Compared with A group, the plasma hormones （Ang Ⅱ , ET-1） in four experimental groups were significantly increased （ P 〈0.01）, but they were reduced in C and E groups compared with A group （ P 〈 0.01）. Compared with A group, the plasma hormone of 6-keto-PGF1a was decreased in four experimental groups （ P 〈0. 01）, but it was improved in C or E group （ P 〈0. 01）. Conclusion：AngⅡ and ET play important roles on the myocardial collagen of postinfarct heart, cilazapril alone can improve myocardial collagen on the noninfarct area after myocardial infarction. Aspirin alone has no effect on the myocardial collagen. Combination of Cilazapril and Aspinn, the effect on myocardial collagen is similar with cilazapril alone.