血管紧张素-(1-7)对兔急性心肌梗死再灌注微血管内皮功能保护的实验研究

Role of Angiotensin-(1-7) in protection of microvascular endothelial function after reperfused acute myocardial infarction in Rabbits

目的探讨血管紧张素-（1-7）[Ang-（1-7）]对急性心肌梗死再灌注时微血管内皮功能的保护作用。方法选用健康新西兰雄性大白兔30只,体重2.5-3.0kg,随机分成以下3组：1）假手术组,2）缺血再灌注（ischemia-reperfusion,I-R）对照组,3）Ang-（1-7）治疗组,每组10只。Ang-（1-7）治疗组经置入式微量泵持续颈静脉给予Ang-（1-7）（25μg·kg^-1·h^-1）3d,假手术组和I-R对照组经微量泵只给予等量的生理盐水。每组均在3d预处理后,冠状动脉左前降支结扎2h,再灌注2h。测定缺血前、后和再灌注2h时血中一氧化氮（nitric oxide,NO）水平,再灌注2h时心肌一氧化氮合酶（nitric oxide synthase,NOS）活性,血循环内皮细胞（CEC）计数,并采用氯化三苯四唑（triphenylte trazolium chloride,TTC）染色观察心肌梗死范围。结果（1）心肌缺血前各组对比,NO在Ang-（1-7）治疗组已显著升高（P〈0.01）;心肌缺血后2h时,各组NO均比缺血前显著降低（P〈0.01）,但在Ang-（1-7）治疗组比I-R对照组显著增高（P〈0.01）;再灌注2h后,各组NO水平均比缺血2h时进一步降低,但在Ang-（1-7）治疗组仍比I-R对照组显著增高（P〈0.01）。（2）再灌注后2h,血循环内皮细胞计数（CEC）,I-R对照组与假手术组相比显著增加[（15.82±8.16）个/mm^3vs.（4.26±1.52）个/mm^3,P〈0.01];而Ang-（1-7）治疗组与I-R对照组相比CEC显著降低[（7.78±3.82）个/mm^3vs.（15.82±8.16）个/mm^3,P〈0.05]并与假手术组无显著差异。（3）心肌NOS活性,与假手术组相比,I-R对照组和Ang-（1-7）治疗组均降低,但在Ang-（1-7）治疗组NOS活性比I-R对照组明显增高（P〈0.05）。（4）心肌梗死面积在I-R对照组为（28.70±5.45）%,而Ang-（1-7）治疗组[（15.46±4.32）%]与之相比则显著降低（P〈0.01）。结论Ang-（1-7）对急性心肌梗死再灌注微血管内皮功能具有保护作用。

Objective To explore the role of Angiotensin-（1-7） [Ang-（1-7）] in protection of microvascular function after reperfused acute myocardial infarction（AMI）. Methods Thirty healthy male New Zealand white rabbits were randomly divided into 3 groups ： （1） Sham operation group; （2） Ischemia-reperfusion group （I-R group） ; （3） Ang-（1-7） group. Intravenous infusion of Ang-（1-7） （25 μg · kg^-1 · h^-1, for Ang-（1-7） group） or saline （for sham operation group and I-R group） was given by minipump for 3 days. After 3 days of pretreatratment, the left coronary artery in the rabbit was ligated for 2 h and loosed subsequently for another 2 h. The serum levels of nitric oxide （NO） were measured before AMI, 2 h after both AMI and reperfusion. The activity of myocardial nitric oxide synthase （NOS） and the number of circulating endothelial cells （CECs） were also determined in 2 h after reperfusion. Myocardial infarction area was measured by triphenyltetrazolium chloride （TTC） method. Results （1） The baseline level of NO was significantly higher in Ang-（1-7） group than in other groups （all P〈0. 01）. After 2 h AMI, NO level was significantly reduced in each group compared with their baseline （all P〈0.01）, but the level of NO was significantly higher in Ang-（1-7） group than in I-R group （P〈0.01）. After 2 h reperfusion, NO was further reduced compare with their values in 2 h AMI, but the level of NO was still significantly higher than in I-R group （P〈0.01） ; （2） After 2 h reperfusion, the number of CECs was significantly increased in I-R group than in sham operation group （15.82 ±8. 16/mm^3 vs. 4.26 ± 1.52/mm^3, P〈 0.01） . The number of CECs was significantly reduced in Ang-（1-7） group than in I-R group （7.78±3.82/mm^3 vs. 15.82±8.16/mm^3, P〈0. 05） and there was no statistic difference between in Ang-（1-7） group and in sham operation group; （3） After 2 h reperfusion, the activity of myocardial NOS was significantly reduced in both Ang-（1-7） group and I-R group compared with sham operation group, but the activity of myocardial NOS was significantly increased in Ang-（1-7） than in I-R group （P〈0. 05） ; （4） Myocardial infarction area was smaller in Ang-（1-7） than in I-R group E（15.46± 4.32）% vs. （28.70±5.45）%, P〈0.01]. Conclusions Ang-（1-7） can protect microvascular endothelial function after reperfused AMI.