心衰大鼠ACE/ACE2表达变化及血管紧张素转换酶抑制剂的干预作用

ACE and ACE2 alterations in congestive heart failure rats and intervention effect of benazepril

目的探讨心肌梗死后心力衰竭大鼠心肌组织ACE/ACE2表达变化及苯钠普利的干预作用。方法结扎大鼠左冠状动脉前降支复制心肌梗死后心衰模型,分为心衰对照组、苯钠普利组、假手术组。喂养2个月后检测血流动力学指标,计算体重与左心室重量指数,RT-PCR方法检测心肌组织ACE和ACE2 mRNA表达,免疫组化检测ACE和ACE2蛋白表达。结果心衰对照组大鼠心肌组织ACE和ACE2的mRNA和蛋白表达均增强(P<0.01),ACE/ACE2比值升高。苯钠普利组大鼠血流动力学指标改善(P<0.01),心肌组织ACE mRNA和蛋白表达下降(P<0.01),ACE2 mRNA和蛋白表达显著增强(P<0.01),ACE/ACE2比值降低。结论心衰大鼠心肌组织ACE和ACE2表达上调,ACE上调更显著,ACE/ACE2比值升高;苯钠普利抑制ACE表达,刺激ACE2表达增强,ACE/ACE2比值下降,这是对该药物作用机制的新解释。

Objective To explore the expressions of ACE/ACE2 in congestive heart failure （CHF） rats after myocardial infarction and the treatment effect of benazepril, an angiotensin converting enzyme inhibitor. Methods The rat heart failure model was induced by acute myocardial infarction （AMI） through ligating the left anterior descending coronary artery. One month after operation, rats were randomized to CHF placebo group and benazepril group. Sham-operated rats were used as the control group. Then 8 weeks later the rats were evaluated for hemodynamic parameters, body mass and left ventricular mass index, ACE and ACE2 mRNA expressions by RT-PCR and their protein expressions by immunohistochemical methods. Results The mRNA and protein expressions of ACE and ACE2 were increased in CHF placebo group than sham-operation group （ P 〈 0. 01 ） , and the ratio of ACE/ACE2 was elevated. The hemodynamic parameters of benazepril group improved significantly than CHF placebo group （P 〈 0.01 ）. Furthermore, the levels of ACE mRNA and protein of benazepril group decreased significantly （P 〈0.01 ） , whereas the level of ACE2 mRNA and protein were increased （P 〈0.01）, therefore, the ratio of ACE/ACE2 decreased. Conclusion The mRNA and protein expressions of ACE and ACE2 were upregulated in CHF rats, and the ratio of ACE/ACE2 was elevated. Administer of benazepril can downregulate ACE expression and upregulate ACE2 expression, so the ratio of ACE/ACE2 decreases, which might be the another intervention mechanism of the drug.