摘要
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.
出处
《中国心血管杂志》
2007年第5期321-324,共4页
Chinese Journal of Cardiovascular Medicine
基金
广东省博士启动基金(No04300348)