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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 50 0 0m模拟高原缺氧 5、1 5和 30d后 ,用碱性磷酸酶 (ALP)组织化学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 1 5d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。左室心肌随着缺氧时间的延长 ,毛细血管密度和C/M比值逐渐增高 ,缺氧30d时毛细血管密度和C/M比值较常压对照组显著增加。原位杂交和免疫组织化学结果显示 ,VEGFmRNA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。
Objective To observe the changes of capillary density and the content of vascular endothelial growth factor (VEGF) and its receptor in myocardium during hypoxia in rats. Methods The rats were subjected to simulated hypoxia for 5, 15, and 30 days on the plateau. The myocardial tissue of the capillaries were visualized by alkaline phosphatase (ALP) histochemistry and analyzed by in situ hybridization and immunohistochemistry Expression of VEGFmRNA, VEGF, FLK and Flt 1 in Myocardial Tissue. Results At 15 days of hypoxia, the ratio of capillary to muscle fibers (C / M) in the unit area of right ventricular myocardium was significantly increased. The capillary density and C / M ratio of left ventricular myocardium gradually increased with the prolongation of hypoxia, and the capillary density and C / M ratio increased significantly at 30th day after hypoxia compared with the control group. In situ hybridization and immunohistochemistry showed that VEGF mRNA mainly existed in cardiomyocytes, while VEGF protein mainly distributed in the cytoplasm, membrane and cardiomyocyte space of cardiomyocytes. The hypoxia in the body when the expression of VEGF in the myocardium generally increased, peaked 5d. FLK and Flt 1 were mainly distributed in microvascular endothelial cells, and there was no significant difference in FLK and Flt 1 expression in each group. Conclusions During the process of hypoxia in rats, left and right ventricular hypertrophy may occur, which may be related to the up-regulation of VEGF expression.