卡维地洛增加心力衰竭大鼠心肌细胞血管紧张素转换酶2

The Effect of Carvedilol on ACE2 Expression in Chronic Heart Failure Rats

目的探讨卡维地洛对心肌梗死后大鼠心肌组织血管紧张素转换酶2(ACE2)的影响。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(CHF)模型,随机分为 CHF 组,卡维地洛组和假手术组。2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(AngⅡ)水平,RT-PCR 方法检测心肌组织 ACE2 mRNA 表达,Western-Blot 方法检测心肌组织 ACE2蛋白表达。结果 CHF 组与卡维地洛组8周死亡率都是20%,而假手术组为0%。卡维地洛明显改善 CHF 大鼠的血流动力学参数(LVEDP,LVSP,+dp/dt_(max)和-dp/dt_(min)),但仍然比假手术组差。CHF 组大鼠循环和心肌组织 Ang Ⅱ水平明显升高[循环AngⅡ:(194±19)比假手术组(132±15)ng/L,心肌 AngⅡ:(6.7±0.4)比假手术组(3.8±0.3)ng/g,P 均<0.01],心肌组织 ACE2 mRNA 和蛋白表达增强[ACE2 mRNA:(1.09±0.07)比假手术组(0.81±0.06),P<0.01;ACE2蛋白:(0.68±0.08)比假手术组(0.54±0.07),P<0.05]。卡维地洛改善大鼠血流动力学指标(P<0.01),下调心肌组织 AngⅡ水平[(6.0±0.5)比 CHF 组(6.7±0.4),P<0.05],心肌组织 ACE2 mRNA 和蛋白表达显著增强[ACE2 mRNA(1.38±0.08)比 CHF 组(1.09±0.07),ACE2蛋白(0.93±0.09)比 CHF 组(0.68±0.08),P 均<0.01]。结论 CHF 大鼠心肌组织 ACE2表达上调,卡维地洛改善心功能同时伴有 ACE2表达增强,这一现象对 CHF 的作用是通过什么机制有待进一步研究。

Objective To explore the effect of carvedilol on ACE2 gene and protein expression in chronic heart failure rats after myocardial infarction. Methods The 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 receive placebo or carvedilol 2 mg/[kg · d）, by gavage. Sham-operated rats were used as the control group. Hemodynamics, body mass and left ventricular mass index, plasma and myocardial level of angiotensin Ⅱ were determined. ACE2 gene and protein expression was assessed by using RT-PCR and Western Blot. Results The mortality of placebo and Carvedilol groups were 20%, compared with 0% in sham operated rats. Carvedilol significantly improved LVEDP, LVSP, ＋dp/dtmax and -dp/dtmin in CHF rats but all the hemodynamics data were still inferior than that of controls. Plasma and myocardial angiotensin Ⅱ level were increased significantly in CHF placebo rats than those of control rats（plasma Ang Ⅱ ： CHF： 194± 19 vs controls： 132± 15 ng/L, myocardium Ang Ⅱ ：CHF： 6.7 ± 0.4 vs control： 3.8 ±0.3 ng/g, P（0.01 ）. ACE2 mRNA and protein were concomitantly in- creased[ ACE2 mRNA：CHF： 1.09 ± 0.07 vs controls： 0.81± 0.06 ; ACE2 protein： CHF： 0.68± 0.08 vs controls： 0. 54±0. 07, P〈0.01 }, Carvedilol significantly improved hemonamic data[ P〈0.01 } and decreased myocardial Ang Ⅱ obviously [Carvedilol： 6.0±0.5 vs CHF： 6.7±0.4, P〈0.05）, while the level of ACE2 mRNA and protein were increased significantly [Carvedilol： ACE2 mRNA： 1.38 ± 0.08 vs CHF： 1.09 ± 0.07, ACE2 protein： Carvedilol： 0.93＋0.09 vs CHF：0.68±0.08,P all〈0.01） . Conclusion ACE2 gene and protein expression were upregulated in CHF rats. Carvedilol accentuate the upregulation of the expression of ACE2. Whether ACE2 upregulation is a compensatory response, a beneficial factor for CHF, or just an associated phenomenon need luther investigation.