猪急性心肌梗死再灌注后微血管内皮细胞损伤及通心络的保护作用

Protective effect of Tong-xin-luo on microvascular endothelium dysfunction in mini-swine model of acute myocardial infarction reperfusion

目的评价猪急性心肌梗死(AM I)再灌注后微血管内皮细胞结构和功能损伤,以及中药通心络的保护作用和机制。方法 30只中华小型猪随机分成假手术组、模型组、小剂量、中剂量和大剂量通心络治疗组,每组6只。建立AM I再灌注模型,观察不同区域心肌组织内细胞黏附分子和内皮细胞间连接蛋白的含量和变化。结果与正常区比较,模型组再灌注区和无再流区P-选择素(P-selectin)、细胞间黏附分子-1(ICAM-1)、血管细胞黏附分子-1蛋白及mRNA水平升高,再灌注区内皮钙黏素(VE-cadherin)、无再流区VE-cadherin和β连环蛋白含量降低。与模型组比较,中剂量组再灌注区和无再流区P-selectin和ICAM-1蛋白降低;大剂量组再灌注区P-selectin、ICAM-1蛋白和mRNA含量降低,无再流区P-selectin蛋白和mRNA及ICAM-1蛋白含量降低。大剂量组再灌注区和无再流区VE-cadherin表达升高。结论中药通心络通过抑制细胞黏附分子的表达,减少中性粒细胞浸润和炎症反应,保护AM I再灌注过程内皮细胞屏障功能完整性。

Objective To assess microvascular endothelium dysfunction after acute myocardial infarction（AMI） and reperfusion,and clarify the protective effect of Tong-xin-luo in mini-swine model.Methods Thirty mini-swines were randomly divided into 5 study groups： sham group,model group,low dose,medium dose and high dose groups of tong-xin-luo pretreated.Contents of P-selectin,ICAM-1,VCAM-1,VE-cadherin,β-catenin and γ-catenin in the myocardium were evaluated after reperfusion.Results Protein and mRNA content of P-selectin,ICAM-1 and VCAM-1 in reperfusion and no-reflow myocardium increased significantly.Compared with that of normal area,expression of VE-cadherin decreased in reperfusion myocardium,while expression of VE-cadherin and β-catenin reduced in no-reflow myocardium.Compared with that of model group,medium dose compound could reduce protein expression of P-selectin and ICAM-1 in reperfusion and no-reflow myocardium.High dose compound could decrease protein and mRNA content of P-selectin and ICAM-1 in reperfusion area,and also reduce protein and mRNA of P-selectin as well as protein of ICAM-1 in no-reflow area.High dose of Tong-xin-luo could enhance the expression of VE-cadherin in both reperfusion and no-reflow myocardium when compared with that of model group.Conclusion Tong-xin-luo could protect endothelium from reperfusion injury and remain the endothelial barrier by reducing adhesion molecular expression and inhibiting neutrophils infiltration.