通心络、卡维地洛、缬沙坦对兔急性心肌梗死晚期再灌注微血管内皮功能及完整性保护作用的对比

 目的：探讨通心络、卡维地洛、缬沙坦对兔急性心肌梗死（AMI）晚期再灌注微血管内皮功能及完整性的保护作用。 方法:选用大耳白兔48只，随机分成以下6组：假手术组、缺血（即AMI）再灌注(I-R)对照组以及通心络、卡维地洛、缬沙坦和抵克力得+阿斯匹林防治组，每组8只。各组灌药3 d后行冠状动脉结扎2 h，再松解2 h。分别测定AMI前、后和再灌注后血一氧化氮(NO)、内皮素（ET）含量，测定再灌注后血循环内皮细胞数（CEC）、梗死面积和心肌灶性出血发生率。结果:①AMI前，通心络组的NO₂^-/NO₃^-显著高于其它各组（均P<0.01），而ET则均无显著差异。AMI后和再灌注后2 h，各组NO₂^-/NO₃^-比AMI前均显著降低（P<0.05,P<0.01），ET均显著增高（P<0.05,P<0.01）；但与I-R组相比，NO₂^-/NO₃^-在通心络组仍显著为高（均P<0.01），且均显著高于其它治疗组（P<0.05,P<0.01）；而ET在通心络和缬沙坦组均显著为低（P<0.05,P<0.01），但比其它治疗组均无显著差异。②I-R组的CEC计数比假手术组显著增高（均P<0.01）；但与I-R组相比，CEC计数在通心络组显著降低（P<0.05），在抵克力得组则显著升高（P<0.05）。③I-R组的 MI面积为24.9%，各治疗组均显著低于I-R组（均P<0.01）。④心肌灶性出血发生率I-R组为62.5%，在通心络和缬沙坦组则显著隆至12.5%和25%（P<0.05,P<0.01）。⑤AMI再灌注后2 h，血NO₂^-/NO₃^-和ET水平分别与MI面积呈显著负相关和正相关（NO₂^-/NO₃^-：r=-0.884,P<0.01；ET:r=0.946，P<0.01）。 结论:① 兔AMI晚期再灌注时，心肌微血管内皮功能及完整性明显受损，伴MI面积增大和心肌灶性出血增加；② 通心络和缬沙坦一样对AMI晚期再灌注时心肌微血管内皮功能及完整性有明显的保护作用，通心络作用可能更优，值得进一步研究。

Protective effects of tongxinluo, carvedilol and valsartan on microvascular endothelial function and integrity after late reperfused AMI in rabbits

AIM:To compare the protective effects of tongxinluo, a Chinese medicine, and carvedilol and valsartan on myocardium microvascular endothelial function and integrity after late reperfusion of acute myocardial infarction (AMI) in rabbits. METHODS:Forty-eight rabbits were randomly assigned to the follo wing groups:(1) sham operated rabbits;(2) ischemia-reperfusion (I-R) controls ;(3) tongxinluo (1.0 g·kg^-1·d^-1);(4) carvedilol (5 mg·kg^-1·d^-1);(5) valsartan (10 mg·kg^-1·d^-1) and (6) ticlopidine + aspirine (30 and 20 mg·kg^-1·d^-1, respectively) groups. After 3 d of drug treatment, 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 (NO₂^-/NO₃^-) and endothelin (ET) at baseline before AMI, 2 h after both AMI and reperfusion were examined. Also, the number of circulating endothelial cells (CEC), MI size and percentage myocardium focal bleeding incidence were determined 2 h after reperfusion. RESULTS:(1) The baseline level of NO₂^-/NO₃^- was significantly higher in tongxinluo group than that in other groups (all P<0.01), whereas the content of ET was not significantly different among the groups. 2 h after both AMI and reperfusion, NO₂^-/NO₃^- was significantly reduced (P<0.05, P<0.01) and ET was significantly increased in each group as compared with their baseline (P<0.05, P<0.01). Yet among the groups, NO₂^-/NO₃^- was still significantly higher and ET was significantly lower in tongxinluo-treated group than that in the other groups (P<0.05, P<0.01). (2) CEC number was significantly increased in I-R controls as compared with sham group (P<0.01), and was significantly reduced in the tongxinluo-treated groups as compared with I-R controls (P<0.05). (3) MI size was significantly reduced in the four treatment groups as compared with I-R controls (all P<0.01). (4) The per centage of myocardium focal bleeding incidence was significantly lower in tongxi nluo and valsartan-treated groups than that in I-R controls (P<0.05, P<0.0 1). CONCLUSION:Tongxinluo as well as valsartan effectively protects myocardium endothelial function and integrity during AMI and late reperfusion, with the effects of tongxinluo being superior.