坎地沙坦抑制小鼠视网膜新生血管的实验研究

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目的探讨坎地沙坦对小鼠视网膜新生血管(Retinal neovascularization,RNV)的抑制作用。方法采用随机对照实验研究,选取7 d龄C57BL/6J新生小鼠40只,随机分为2组:高氧组和坎地沙坦组,每组20只。坎地沙坦组和高氧组小鼠建立氧诱导视网膜病变模型,出氧箱后,每日分别腹腔注射坎地沙坦40 mg/kg和等量生理盐水,连续5 d。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检测视网膜血管紧张素Ⅱ(Angio-tensinⅡ,AngⅡ)和血管内皮细胞生长因子(Vascular endothelial growth factor,VEGF)蛋白的表达。结果荧光素血管灌注视网膜铺片:高氧组可见大量新生血管丛,伴明显荧光渗漏,坎地沙坦组较高氧组视网膜新生血管减少,荧光渗漏减轻。突破视网膜内界膜的血管内皮细胞核数:坎地沙坦组较高氧组减少,差异具有统计学意义(P<0.01)。视网膜AngⅡ蛋白表达水平:坎地沙坦组较高氧组下调,差异具有统计学意义(P<0.01)。视网膜VEGF蛋白表达水平:坎地沙坦组较高氧组下调,差异具有统计学意义(P<0.01)。结论早期应用坎地沙坦可一定程度抑制RNV形成。 Objective To investigate the inhibitory effect of candesartan on retinal neovascularization (RNV) in mice. Methods A randomized controlled trial was conducted. Forty neonatal C57BL / 6J mice, 7 days old, were randomly divided into 2 groups: hyperoxia group and candesartan group, 20 in each group. The model of oxygen induced retinopathy was established in candesartan group and hyperoxia group. After experiencing oxygen box, candesartan 40 mg / kg and normal saline were injected intraperitoneally daily for 5 consecutive days. The morphological changes of retinal vessels were observed by fluorescein perfusion of retina and the retinal vascular morphology was observed. The retinal tissue sections were made and stained with hematoxylin and eosin (HE) to count the number of vascular endothelial cells that broke the inner limiting membrane of the retina. Angiotensin Ⅱ (Angio-tensinⅡ, Ang Ⅱ and Vascular endothelial growth factor (VEGF) protein expression. Results Fluorescein perfusion retinal lamina: a large number of neovascularization can be seen in the hyperoxia group, accompanied by significant fluorescence leakage, retinal neovascularization was reduced in the candesartan group compared with the hyperoxia group, and the fluorescence leakage was alleviated. Break through the inner limiting membrane of the vascular endothelial cells nucleus number: candesartan group decreased compared with hyperoxia group, the difference was statistically significant (P <0.01). The level of AngⅡ protein in retina was lower in candesartan group than in hyperoxia group (P <0.01). Retinal VEGF protein expression levels: candesartan group was lower than the high oxygen group, the difference was statistically significant (P <0.01). Conclusion Candesartan can inhibit the formation of RNV to a certain extent.
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