激活的巨噬细胞心肌移植改善大鼠心肌梗死后心室重塑作用

摘要/Abstract

摘要： 目的探讨苯妥英钠和巨噬细胞介导的旁分泌机制对心肌梗死后血管新生和心室重塑的影响。方法贴壁法培养Wistar大鼠腹腔巨噬细胞，并以苯妥英钠进行预刺激。建立Wistar大鼠心肌缺血再灌注模型，分为对照（AMI）组、苯妥英钠（PHT）组、单纯巨噬细胞移植（MΦ）组、苯妥英钠预刺激的巨噬细胞移植（MΦ-PHT）组及假手术组。术后第7天和第28天，分别取大鼠心室进行组织学分析测定膨展指数、纤维面积、非梗死区心肌细胞横截面积（CSA）、梗死区小动脉密度和毛细血管密度，术后7天采用Western blot分析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组、MΦ组和MΦ-PHT组术后第28天膨展指数、纤维面积和非梗死区CSA均显著减少（P <0.05），而小动脉密度显著增加（P <0.05）；术后28天MΦ-PHT组纤维面积显著小于MΦ组（P＜0.05）；MΦ-PHT组较MΦ组术后第7天和第28天小动脉密度和毛细血管密度有增加趋势；MΦ-PHT组较MΦ组术后第7天梗死区VEGF、b-FGF蛋白表达水平均显著增强（P <0.05）。结论苯妥英钠可能通过激活巨噬细胞介导旁分泌效应，上调与血管新生密切相关的生长因子的蛋白表达水平，促进组织血管新生，改善心肌梗死后心室重塑。

关键词: 巨噬细胞, 苯妥英钠, 心肌梗死, 血管新生, 心室重塑

Abstract: Objective To investigate the mechanism of the paracrine effect of phenytoin (PHT) and macrophage in the angiogenesis and ventricular remodeling after myocardial infarction (MI). Method The peritoneal macrophages were adherently cultured, and parts of cultured macrophages were pre-stimulated by PHT. The survival animals induced experimental ischemia-reperfusion (I/R) were randomly distributed into Sham group, control (AMI) group, Phenytoin (PHT) group group, macrophage (MΦ) group, phenytoin pre-stimulating macrophage (MΦ-PHT) group. At the 7th and 28th day after the induction of I/R, histology examination were analyzed including index of expansion, fiber area, arterioles density, capillary density in infarct region and cardiocyte cross-sectional area (CSA) in non-infarct zone. The levels of protein expression of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF) within infarct region 7 days after MI were determined by Western blot. Result Compared with AMI group, Index of Expansion, fiber area and CSA in non-infarct zone at 28th day were all decreased in PHT group, MΦ group and MΦ-PHT group (P <0.05), while arteriole density in infarct zone had increased (P <0.05). Fiber area of MΦ-PHT group at 28th day was fewer than MΦ group (P <0.05). Compared with MΦ group, capillary density and arteriole density in infarct zone at 7th and 28th day had increasing tendency. The levels of VEGF, bFGF protein expression in infarct zone at 7th day in MΦ-PHT group were more than MΦ group (P <0.05). Conclusion Phenytoin may promote angiogenesis in infarct zone and improve ventricular remodeling after MI through stimulating macrophages, which up-regulate the growth factors involved in the angiogenesis through the paracrine effect.

李贺. 激活的巨噬细胞心肌移植改善大鼠心肌梗死后心室重塑作用[J]. 基础医学与临床, 2011, 31(11): 1267-1272.

He LI. Ex vivo activated macrophages myocardial transplantation improve the ventricular remodeling of the infarcted heart induced by ischemia/reperfusion[J]. Basic & Clinical Medicine, 2011, 31(11): 1267-1272.

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