Akt抑制剂对氧诱导视网膜新生血管形成的作用

Application of Akt inhibitor in the oxygen-induced retinopathy

摘要:

目的：观察Akt抑制剂对低氧环境下视网膜新生血管形成的抑制作用，探讨Akt活性的抑制对于新生血管抑制的作用。方法：将鼠龄为7 d的C56BL/6J小鼠14只置于浓度为（75±2）%高氧舱环境中生活5 d，然后返回正常氧环境中。14只小鼠于出氧舱后当日被随机平均分为实验组和对照组各7只，实验组小鼠玻璃体腔内注射1.5 μl Akt抑制剂，对照组小鼠玻璃体腔内注射1.5 μl PBS。在P17，实验组和对照组小鼠FITC-Dextran左心室造影视网膜铺片了解视网膜的血管形态的改变以及小鼠组织学切片观察突破视网膜内界膜的血管内皮细胞核数量。结果：视网膜铺片结果显示实验组与对照组相比较，视网膜可见新生血管芽，但是新生血管丛数量及面积明显减少，荧光渗漏明显减轻，但无灌注区无明显的减小；组织学切片结果表明与对照组相比较，Akt抑制剂注射实验组突破视网膜内界膜的血管内皮细胞核数量明显减少，实验组突破视网膜内界膜的血管内皮细胞核数量为（14±3.0）个，对照组为（55±3.0）个，差异具有统计学意义（P=0.001）。结论：在缺氧环境下运用Akt抑制剂能够抑制视网膜新生血管的发生，但Akt抑制剂不减少无灌注区的面积。

Abstract:

Objective：To examine whether Akt inhibitor treatment during the phase of oxygen-induced retinopathy helps to prevent retinal neovascularization. Methods：Seven-day-old C56BL/6J mice were exposed to（75±2）% oxygen for 5 d，then returned to the room air to induce rentinal neovascularization. Fourteen mice were equally randomized into control group and experiment group. On P12，1.5 μl Akt inhibitor was injected into vitreous cavity of mice in experiment group and PBS was injected into mice in control group. Retinal neovascularization was analyzed with FITC-Dextran and histological analysis on P17. Results：Mice treated with Akt inhibitor had a reduced pathologic neovascular tufts and fluorescence leakage compared with those of PBS controls. For the area of capillary-free，no difference was seen between experiment group and control group. The histological analysis showed that neovascular nuclei protruding into viteous cavity were decreased in experiment group compared with those in control group. Conclusion：Akt inhibitor treatment protects the retina from vessel pathological proliferation，but cannot protect the retina from vessel loss.