血管紧张素Ⅱ和血管内皮生长因子在视网膜新生血管中的表达及意义

Expression and significance of angiotensin Ⅱ and vascular endothelial growth factor in retinal neovascularization

目的:探讨血管紧张素II(angiotensin II,Ang II)和血管内皮生长因子(vascular endothelial growth factor,VEGF)在视网膜新生血管发生发展中的作用。方法:随机对照实验研究。选取7d龄C57BL/6J新生小鼠40只,随机分为2组:正常对照组和高氧模型组,每组20只,高氧模型组建立氧诱导视网膜病变模型。采用荧光素血管灌注视网膜铺片观察视网膜血管形态学改变;制作视网膜组织切片并进行HE染色计数突破视网膜内界膜的血管内皮细胞核数;采用Western blot检测视网膜Ang II和VEGF蛋白的表达。采用独立样本t检验和Pearson相关分析进行统计学分析,以P<0.05作为差异具有统计学意义。结果:荧光素血管灌注视网膜铺片:高氧模型组较正常对照组可见大量新生血管丛,伴明显荧光渗漏。突破视网膜内界膜的血管内皮细胞核数:高氧模型组(43.23±2.57)个较正常对照组(1.37±0.93)个明显增多,差异具有统计学意义(P=0.00)。视网膜Ang II蛋白表达水平:高氧模型组(0.365±0.004)较正常对照组(0.035±0.003)明显上调,差异具有统计学意义(P=0.00)。视网膜VEGF蛋白表达水平:高氧模型组(0.372±0.004)较正常对照组(0.049±0.007)明显上调,差异具有统计学意义(P=0.00)。结论:Ang II促血管生成的作用与VEGF存在明确的联系,Ang II通过上调VEGF参与视网膜新生血管的形成。

·AIM：To investigate a possible role for the angiotensin Ⅱ（Ang Ⅱ）and vascular endothelial growth factor（VEGF）in the development of retinal neovascularization.·METHODS：It was a random control experimental study.Forty seven-day-old C57BL/6J mice were divided into two groups randomly including normal control group and hyperoxia model group.Hyperoxia model group were exposed to 75% oxygen to establish a model of oxygen-induced retinopathy.Fluorescent angiography was used to assess the vascular pattern of retina.The proliferative neovascular response was quantified by counting the nuclei of new vessels extending from the retina into the vitreous in cross-sections.Ang II and VEGF protein levels in retinas were measured by Western blot.Significant differences between groups were evaluated by independent-samples t test and Pearson correlation analysis.Statictical difference was considered significant at a P value less than 0.05.·RESULTS：Fluorescent angiography presented increasing neovascular tufts with fluorescein leakage in hyperoxia model group compared to the normal control group.The number of endothelial cells of new vessels extending from retina to vitreous were increased significantly in hyperoxia model group（43.23±2.57）as compared with normal control group（1.37±0.93）（P=0.00）.The expression of Ang II protein in retinas were increased significantly in hyperoxia model group（0.365±0.004）compared with normal control group（0.035±0.003）（P=0.00）.The expression of VEGF protein in retinas were increased significantly in hyperoxia model group（0.372±0.004）compared with normal control group（0.049±0.007）（P=0.00）.·CONCLUSION：There is specific relation between Ang II and VEGF in angiogenesis promoting effect.Ang II participate in the occurrence and development of retinal neovascularization via the upregulation the expression of VEGF.·