氯沙坦、螺内酯及二者联用对心肌梗死大鼠早期基质金属蛋白酶抑制剂的影响

Effects of losartan,spironolactone and combination therapy on metalloproteinases inhibitors during early period after myocardial infarction in rats

目的观察氯沙坦、螺内酯及其二者合用对急性心肌梗死早期基质金属蛋白酶抑制剂的影响,探讨其作用机制,为临床提供依据。方法建立大鼠的心肌梗死模型,早期应用醛固酮受体拮抗剂螺内酯20mg.d-1.kg-1,血管紧张素-ⅡATI受体拮抗剂氯沙坦10mg.d-1.kg-1及其二者合用进行干预与心肌梗死组比较,利用逆转录-PCR技术(RT-PCR)的方法,观察心肌基质金属蛋白酶抑制剂(TIMP-1)mRNA的表达。结果急性心肌梗死后7d氯沙坦螺内酯及二者联用组心肌基质金属蛋白酶抑制剂(TIMP-1)mRNA表达较心肌梗死组及假手术组明显升高(P<0.01)。结论氯沙坦、螺内酯及其二者联用有助于改善急性心肌梗死预后。

Objective To observe the effects of losartan,spironolactone and combination therapy of both drugs on metalloproteinases inhibitors at early period after myocardial infarction in rats,and to detect the levels of metalloproteinase-1（TIMP-1）mRNA by RT-PCR,in order to explore its action mechanism to provide the theoretical basis for clinical treatment.Methods The animal models of myocardial infarction were established,then the rats were treated by early application of aldosterone receptor antagonist-spironolactone 20mg·d-1·kg-1,angiotensin-Ⅱ ATI receptor antagonist-losartan 10mg·d-1·kg-1 respectively,and both of them to co-intervent the rats with myocardial infarction.The expressions of TIMP-1 mRNA were detected by RT-PCR.Results The losartan,spironolactone and both of them increased significantly the expression of inhibitors of TIMP-1 mRNA 7 days after acute myocardial infarction,as compared with that in model group and sham-operation group（P〈0.01）.Conclusion The losartan,spironolactone and combined both drugs can contribute to improve the prognosis of acute myocardial infarction.