通心络预给药2小时对猪急性心肌梗死再灌注后心肌微血管内皮结构完整和无再流的保护作用

Effects of tongxinluo on mini-swine vascular endothelial integrity and myocardial no-reflow in early reperfusion of acute myocardial infarction

目的评价冠脉再通前2h给予不同剂量通心络对猪急性心肌梗死（AMI）缺血再灌注后心肌微血管结构完整和无再流变化的疗效。方法中华小型猪40只，分成假手术组、AMI对照组、通心络治疗组：小剂量（0．1g/kg）、中剂量（0．2g／kg）和大剂量（0．4g／kg），每组8只。冠状动脉前降支阻断1．5h，再灌注3h建立AMI缺血再灌注动物模型。各通心络治疗组于AMI缺血再灌注前2h行灌胃给药。测定并比较各组再灌注后3h正常区、再灌注区、无再流区心肌组织中血管内皮钙黏连蛋白、8连环蛋白、基质金属蛋白酶（MMP）-2和9水平变化。于AMI1．5h和再灌注3h行心肌声学造影（MCE），测定并比较心肌无再流面积变化。结果（1）与正常区相比，对照组再灌注区和无再流区心肌组织中血管内皮钙黏连蛋白和B连环蛋白水平均显著降低，而MMP-2、9水平均显著升高（P均〈0．05），且无再流区变化更显著（P均〈0．05）；（2）大剂量通心络能够显著升高再灌注区和无再流区血管内皮钙黏连蛋白和[（22．2±3．2）％比（32．0±3．9）％和（14．5±2．8）％比（28．3±2．2）％]，B连环蛋白[（20．5±3．5）％比（27．3±2．9）％和（13．3±2．1）％比（20．6±2．4）％]，同时显著降低再灌注区和无再流区MMP-2[（48．3±4．1）％比（29．4±3．5）％和（57．3±4．3）％比（38．2±4．0）％l，MMP-9[（55．6±4．0）％比（34．3±3．5）％和（62．4±4．8）％比（44．4±4．1）％，P均〈0．05]；（3）大剂量通心络能够显著缩小再灌注后3h心肌无再流区面积[（6．6±1．7）cm^2比（4．8±1．5）cm^2，P〈0．05]；和心肌无再流范围[（90．8±3．8）％比（71．4±4．1）％，P〈0．05]。结论AMI缺血再灌注前2h预给予大剂量通心络对心肌微血管内皮结构完整和心肌无再流有明确保护作用，为通心络的临床应用提供了实验依据。

Objective To assess the effects of tongxinluo on vascular endothelial integrity and myocardial no-reflow in early reperfusion of acute myocardial infarction. Methods Forty mini-swines were divided into five groups randomly, sham group, control group, low dose （0. 1 g/kg）, medium dose （0. 2 g/ kg） and high dose （0. 4 g/kg） groups of Tongxinluo. It was administered at 2 hours pre-reperfusion. Animals except in sham group were subjected to 1.5 hour of coronary occlusion followed by 3 hours of reperfusion. Content of VE-cadherin, 13-catenin, matrix metalloproteinase （MMP） -2 and 9 in myocardium were evaluated; no-reflow area was examined with myocardial contrast echocardiography （MCE） at 1.5 hour of AMI and 3 hours of reperfusion. Results （ 1 ） Compared with that of normal myocardium, content of VE- cadherin and 15-catenin decreased in reperfusion and no-reflow myocardium while MMP-2 and 9 increased significantly （ all P 〈 0. 05 ） ; （ 2 ） Compared with that of control group, a high dose of Tongxinluo could increase significantly the content of VE-eadherin in both reperfusion and no-reflow myocardium, （22. 2 ± 3.2）% vs （32.0±3.9）% and （14.5 ±2.8）% vs （28.3 ±2.2）% respectively, 13-catenin, （20.5±3.5）% vs （27.3 ±2.9）% and （13.3 ±2. 1）% vs （20.6 ±2.4）% ,while reduce MMP-2, （48.3 ± 4.1）% vs （29.4±3.5）% and （57.3 ±4.3）% vs （38.2±4.0）% respectively, MMP-9, （55.6± 4.0）% vs （34.3±3.5）% and （62.4±4.8）% vs （44.4±4.1）%,allP〈0.05; （3） Compared with that of control group, a high dose of Tongxinluo could reduce significantly both no-reflow area, （6. 6 ± 1.7 ） cm2vs （4.7±1.5）em2, P〈0.05, and percentage（90.8±3.8）% vs （71.4±4.1）%, P〈0.05, at3 hours of reperfusion. Conclusion A high dose of tongxinluo could effectively maintain the integrity of vascular endothelium and attenuate no-reflow area in early reperfusion of acute myocardial infarction.