缺氧大鼠心肌毛细血管密度与VEGF变化的研究

目的 观察大鼠在缺氧习服过程中心肌组织毛细血管密度和血管内皮细胞生长因子（VEGF）及其受体的变化规律。方法 大鼠在5000m模拟高原缺氧5、15和30d后，用碱性磷酸酶（ALP）组织化学表达方法显示心肌组织毛细血管并进行图像分析；用原位杂交和免疫组织化学技术观察心肌组织中VEGFmRNA、VEGF、FLK和Flt-1蛋白表达情况。结果 缺氧15d时，右室心肌单位面积内毛细血管数与肌纤维数的比值（C／M）显著增高。原位杂交和免疫组织化学结果显示，VEGF mRNA 主要存在于心肌细胞中，而VEGF蛋白主要分布于心肌细胞的胞浆、胞膜及心肌细胞间隙中。机体缺氧时心肌组织中VEGF的表达普遍增强，5d时达高峰。FLK和Flt-1主要分布于心肌细胞的胞浆、胞膜及心肌细胞间隙中。机体缺氧时心肌组织中VEGF的表达普遍增强，5d时达高峰。FLK和Flt-1主要分布于微血管内皮细胞，各组中FLK和Flt-1表达无显著差异。结论 大鼠在缺氧习服过程中，左、右室心肌毛细血管出现增生，其机制可能与VEGF的表达上调有关。

Changes of capillary density and VEGF in myocardium of rats during acclimation to hypoxia

Objective To study the changes of myocardial capillary density and vascular endothelial growth factor (VEGF) and its receptors FLK/Flt 1 in rat during acclimation to hypoxia. Methods Myocardial capillary density (CD) and capillary/myocyte ratio (C/M) was assayed by alkaline phosphatase histochemical method in the rats for 5, 15 or 30 d hypobaric hypoxic exposure (5 000 m). VEGF and its receptors FLK/Flt 1 were examined by in situ hybridization and/or immunohistochemical method. Results After hypoxic exposure for 15 or 30 d, the C/M ratio were significantly increased in both ventricles while the CD remained unchange in the right ventricle. VEGF mRNA was found in the cytoplasm of the myocyte and VEGF protein primarily located in myocyte and in the interstitial tissue; VEGF receptors, FLK and Flt 1, were shown mainly in endothelial cells of capillary. Compared with control group, expression of VEGF in hypoxic rats was obviously up regulated and reached the peak at 5th day after exposured to hypoxia. Conclusion Neovascularization may occur in both ventricles in rat during acclimation to hypoxia. The up regulation of VEGF expression might play roles in this process.