通心络持续干预对猪急性心肌梗死再灌注晚期微血管再生的影响

Sustained Tongxinluo Therapy on Swine Microvascular Angiogenesis at the First Week after Acute Ischemia and Reperfusion

目的研究通心络持续干预对猪急性心肌梗死(AMI)再灌注后7天心肌微血管再生的影响。方法中华小型猪40只,随机分为假手术组、对照组、小剂量(0.1g/kg)、中剂量(0.2g/kg)和大剂量(0.4g/kg)通心络组,每组8只。冠状动脉前降支阻断90 min,再灌注120 min建立缺血再灌注动物模型,各通心络组于冠脉阻断前按双倍常规剂量灌胃给药1次,之后按各常规剂量每日喂食给药至第7天。通过原位杂交检测各组心肌梗死区、边缘区和正常区内皮型一氧化氮合酶(eNOS)和胎肝激酶-1(FLK-1)mRNA水平;Western Blot检测eNOS、FLK-1蛋白表达;免疫组化α-肌动蛋白和血小板内皮黏附分子-1双染色法测定心肌微血管密度。结果与对照组相比,各通心络组显著增加梗死区微血管内皮eNOS和FLK-1 mRNA及蛋白水平表达,同时在梗死区显著增加新生微血管密度,且大剂量通心络疗效更显著。结论持续应用通心络能够促进AMI再灌注后晚期心肌微血管再生,且对梗死区心肌效果更加显著。

Objective To investigate the effect of sustained therapy of Tongxinluo on microvascular angiogenesis at the first week after ischemia and reperfusion in swine with acute myocardial infarction(AMI).Methods Forty mini-swine were randomly divided into sham operated,control,low-,midand high-dose Tongxinluo groups(n=8).The AMI and reperfusion model was constructed.Pathologic myocardial tissue was collected at 7-day after acute ischemia and reperfusion.eNOS and FLK-1 mRNA and protein expression,as well as microvessel density was detected with in situ hybridization(ISH),Western blot analysis and dual immunohistochemistry separately.Results Compared to control group,Tongxinluo significantly increased both mRNA and protein expression of eNOS and FLK-1 in the infarcted area,while the microvessel density increased in both infarcted and marginal area.Conclusion Tongxinluo can increase microvascular angiogenesis at the first week after AMI reperfusion,especially in the infarcted area.