激活的巨噬细胞心肌移植改善大鼠缺血再灌注引起的心肌梗死后心室重塑作用

Ex vivo activated macrophages myocardial transplantation improves the ventricular remodeling of the infarcted heart induced by ischemia/reperfusion

目的观察激活的巨噬细胞(MΦ)心肌移植的旁分泌效应对心肌梗死(MI)后心肌组织修复作用,探讨MΦ心肌修复机制。方法用苯妥英钠(PHT)激活培养的Wistar大鼠腹腔MΦ后进行心肌缺血/再灌注心肌梗死模型Wistar大鼠心肌移植,分为急性心肌梗死(AMI)对照(AMI)、PHT腹腔注射、MΦ移植(MΦ)、激活的MΦ移植(MΦ-PHT)及假手术组。于移植后第7、28天检测各组模型动物心室膨展指数、纤维面积、非梗死区心肌细胞横截面积(CSA)、梗死区小动脉/毛细血管密度,用Western blot分析术后7 d天梗死区血管内皮生长因子(VEGF)、碱性成纤维细胞生长因子(bFGF)蛋白表达水平。结果与AMI组比较,PHT、MΦ、MΦ-PHT组术后28 d膨展指数、纤维面积、非梗死区CSA均显著减少(P<0.05),小动脉密度显著增加(P<0.05);与MΦ组比较,移植激活的MΦ大鼠7 d梗死区VEGF、b-FGF蛋白表达水平均显著增高(P<0.05),术后7、28 d小动脉密度/毛细血管密度增加;术后28 d心肌纤维面积显著缩小(P<0.05)。结论 MI后早期心肌移植激活的巨噬细胞可能通过旁分泌细胞因子,促进组织血管新生,改善心肌梗死后心室重塑。

Objective To explore repairing function of infarcted myocardium and the mechanisms responsible for the effects of myocardial transplantation of activated macrophages（MΦ） in a rat myocardial infarction（MI） model induced by ischemia/reperfusion（I/R）.Methods The animals were randomly distributed into sham group,control group（AMI）,phenytoin（PHT） intraperitoneal injection group（PHT）,MΦ transplant group（MΦ）,and activated macrophage transplant（MΦ-PHT） group.The macrophages activated by PHT were transplanted into myocardium of the model by direct injection.At the 7th and 28th day after MI,index of expansion,fibrotic area,arterioles and capillary density in infarct zone and cardiocyte cross-sectional area（CSA） in non-infarct zone were analyzed by histologic methods.The levels of protein expression of vascular endothelial growth factor（VEGF）,basicfibroblast growth factor（bFGF） within infarct zone at 7 d after MI were determined by Western blot analysis.Results Compared with AMI group,index of expansion,fibrotic area and CSA in non-infarct zone at 28th day all decreased（P0.05） and arteriole density in infarct zone increased（P0.05） in PHT,MΦ and activated MΦ group.Fibrotic area of activated MΦ group at 28th day was smaller than that of MΦ group（P0.05）.Compared with MΦ group,capillary and arteriole density in infarct zone at 7th and 28th day showed increased in activated MΦ group.The levels of VEGF,bFGF expression in infarct zone at 7th day in activated MΦ group were higher than in MΦ group（P0.05）.Conclusions Early myocardial transplantation of activated MΦ may attenuate the ventricular remodeling of MI induced by I/R,which might involve with angiogenesis induced by the growth factors secreted by MΦ transplanted.