通心络预给药2h对猪急性心肌梗死再灌注后心肌无再流和细胞因子变化的影响

Effect of Tongxinluo on Mini-swine Cytokines and Myocardial No-reflow in Early Reperfusion of Acute Myocardial Infarction

目的评价急性心肌梗死(AMI)猪缺血再灌注前2 h给予通心络对血清细胞因子水平和心肌无再流变化的干预效果。方法中华小型猪40只,随机分成假手术组、AMI对照组、通心络小剂量(0.1 g/kg)、中剂量(0.2 g/kg)和大剂量(0.4 g/kg)组,每组各8只。冠状动脉前降支阻断1.5 h,再灌注3 h建立AMI再灌注动物模型。各通心络治疗组于AMI缺血再灌注前2 h行灌胃给药。测定并比较各组AMI前、AMI 1.5 h、再灌注后3 h血清细胞因子水平变化。于AMI 1.5 h和再灌注3 h行心肌声学造影(myocardial contrast echocardiography,MCE),测定并比较心肌无再流面积变化。结果(1)与对照组比较,仅大剂量通心络组在AMI 1.5 h P-选择素(P-selectin)、细胞间黏附分子-1(ICAM-1)水平显著降低(均P<0.05),而再灌注后3 h P-选择素、细胞间黏附分子-1、血管细胞黏附分子-1(VCAM-1)、白细胞介素-6(IL-6)水平均显著降低(均P<0.05),白细胞介素-10(IL-10)水平显著升高(P<0.05);(2)与对照组比较,大剂量通心络能够显著缩小再灌注后3 h心肌无再流区面积[分别为(6.59±1.73)cm2、(4.68±1.53)cm2,P<0.05]。中小剂量组则差异无统计学意义。结论在AMI猪缺血再灌注前2 h予大剂量通心络可显著降低再灌注后细胞黏附和促炎症因子水平,调高抗炎症因子水平,并缩小心肌无再流面积,为临床应用提供了实验基础。

Objective To assess the effect of Tongxinluo on cytokines and myocardial no-reflow in early reperfusion of acute myocardial infarction（AMI）.Methods Forty mini-swine 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） group of Tongxinluo（which were administered 2 h before reperfusion）,eight swine in each group.Animals except those in the sham group were subjected to 1.5 h of coronary occlusion followed by 3 h of reperfusion.Serum contents of P-selectin,intercellular adhesion molecule 1（ICAM-1）,vascular cell adhesion molecule 1（VCAM-1）,interleukin 6（IL-6） and interleukin 10（IL-10）,as well as myocardial contrast echocardiography（MCE） were evaluated at baseline,and after 1.5 h of AMI and 3 h of reperfusion.Results（1） Compared with that of the control group,high dose of Tongxinluo could reduce serum contents of P-selectin and ICAM-1 at 1.5 h of AMI（all P〈0.05）,and P-selectin,ICAM-1,VCAM-1,and IL-6 at 3 h of reperfusion significantly（all P〈0.05）,accompanied by significantly elevated IL-10（P〈0.05）.（2） Compared with that of control group,high dose of Tongxinluo could reduce no-reflow area at 3 h of reperfusion significantly [（6.59±1.73）cm2 vs（4.68±1.53）cm2,P〈0.05].Conclusion High dose of Tongxinluo could effectively reduce serum contents of adhesion and pro-inflammatory cytokines,regulate anti-inflammatory factor levels,and attenuate no-reflow area in the early reperfusion of AMI.It thus provided experimental basis for its clinical application.