靶向超声介导抗细胞间黏附因子-1单克隆抗体对大鼠心肌缺血再灌注损伤的实验性研究

目的探讨靶向超声能否提高抗细胞间黏附因子-1单克隆抗体对大鼠心肌缺血再灌注损伤的保护作用。方法将60只心肌缺血的雄性SD大鼠分为3组,第1组为超声介导抗细胞间黏附因子-1单克隆抗体定向于受损心肌组,第2组为单纯抗细胞间黏附因子-1单克隆抗体组;第3组为对照组。每组又分为24h后处死组和14d后处死质量分数组,每小组为10只。处死后分别行坏死区中性粒细胞记数,梗死区质量分数测定,免疫组织化学检测缺血心肌中的VEGF蛋白表达,缺血心肌区域毛细血管记数,观察用药前后心电图ST段改变。结果24h处死组超声介导组坏死区中性粒细胞平均记数少于单纯用药组,超声介导组梗死区面积明显小于单纯用药组。14d后处死组超声介导组梗死区重量比明显小于单纯用药组,且有大量VEGF蛋白阳性反应的棕褐色颗粒。结论超声介导微泡造影剂携带抗细胞间黏附因子-1单克隆抗体能提高局部药物浓度,减少中性粒细胞在缺血心肌的浸润,减少组织再损伤,促进缺血区毛细血管再生,减少心肌梗死面积。

Experiment Study on Targeted Ultrasound Deliver Monoclonal Antibody to Intercelluler Adhesion Molecule-1 to Myocardial Ischemia-Reperfusion Injury of Rats

Objective To study the cardioprotective effect of targeted ultrasound delivering monoclonal antibody to intercelluler adhesionmolecule-1 to myocardial ischemia-reperfusion injury of rats.Methods 60 male SD rat models of myocardial ischemia_reperfusion injury (I/R) were divided into 3 groups.5% sonicated human albumin microbubble of attached with monoclonal antibody to interceller adhesionmolecule-1 were infused into the tail vein of rats with or without simultaneous ultrasound destruction microbubbles.The third group used as control group.Every group was divided into two groups again.One group(24 h group) were killed after 24 hours and another group(14 days group) were killed after 14 days and examined for VEGF protein expression by immunohistochemical technique.Microvascular density(MVD) and Polymorphonuclears(PMN) were counted in the infarcted area.The area of myocardial necrosis was measured.Results In 24 h group the infiltration of PMN and the area of myocardial necrosis received ultrasound mediated microbubbles was less than the groups without ultrasound mediated.In 14 days group VEGF protein expression and MVD were higher in group which were received ultrasound mediated microbubble destruction for delivering monoclonal antibody than without ultrasound mediated group and in controls.Conclusions Targeted ultrasound can increase the density of monoclonal antibody to intercelluler adhesion molecule-1 in the area of myocardial ischemia,decrease the infiltration of PMN,reduce myocardial ischemia-reperfusion injury,improve myocardial ischemia and reduce the area of myocardial infarction.