心力衰竭大鼠ACE/ACE2相互负向调节及卡维地洛的作用

Relationship between ACE/ACE2 in congestive heart failure rats and effect of carvedilol

目的探讨心肌梗死后心力衰竭大鼠心肌组织血管紧张素转化酶(angiotensin converting enzyme,ACE)与ACE2相互负向调节及卡维地洛的作用。方法结扎大鼠左冠状动脉前降支复制心肌梗死后心力衰竭模型,随机分为心力衰竭组,卡维地洛组和假手术组;喂养2个月后检测血流动力学指标,计算左心室质量指数;放射免疫法测定心肌组织和血浆血管紧张素Ⅱ,逆转录聚合酶链反应检测心肌组织ACE和ACE2mRNA表达;蛋白质免疫印迹法检测心肌组织ACE和ACE2蛋白表达。结果心力衰竭组大鼠循环和心肌组织血管紧张素Ⅱ水平明显升高(P<0.01),心肌组织ACE和ACE2的mRNA和蛋白表达均增强(P<0.05,P<0.01),ACE/ACE2升高。卡维地洛组大鼠血流动力学指标改善(P<0.01),心肌组织血管紧张素Ⅱ水平下调(P<0.05),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降低。结论心力衰竭大鼠心肌组织ACE和ACE2表达上调,ACE/ACE2升高;卡维地洛抑制ACE表达,增强ACE2表达,ACE/ACE2比值下降。

Objectives To explore the relationship between ACE/ACE2 in congestive heart failure rats after myocardial infarction and the treatment effect of Carvedilol. 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 carvedilol group. Sham-operated rats were used as the control group. Then we evaluates the following indexes at 8th week ： （ 1 ） Hemodynamics ; （2） Body mass and left ventricular mass index;（3）The circulate and cardiac level of angiotensin Ⅱ;（4）ACE and ACE2 gene and protein expression using RT-PCR and Western Blot. Results The cirlutation and cardiac angiotentin Ⅱ level were increased significantly in CHF placebo group than sham-operation group （P 〈 0.01）, The ACE and ACE2 mRNA and protein were increased in CHF placebo group than sham-operation group （P〈0.05, P〈 0.01 ） , the ratio of ACE/ACE2 was elevated. The hemodynamies parameters of carvedilol group improved significantly than CHF placebo group （P 〈 0.0l ）. The Ang Ⅱ level of carvedilol group was decreased obviously compared with CHF placebo group（P 〈 0.05）. The level of ACE mRNA and protein were decreased significantly in carvedilol group （P 〈 0.01）. The level of ACE2 mRNA and protein were increased most significantly in carvedilol group （P 〈 0.01 ）. The ratio of ACE/ACE2 was decreased. Conclusions The ACE and ACE2 gene and protein expression were up-regulated in CHF rats, the ratio of ACE/ACE2 was elevated. Carvedilol can down-regulate the expression of ACE and up-regulate the expression of ACE2, then the ratio of ACE/ACE2 decrease. This is the new explanation of the mechanism of the drug.