血管内皮细胞生长因子反义寡聚脱氧核苷酸对视网膜新生血管的影响

目的探讨血管内皮细胞生长因子(vascular endothelial growth factor,VEGF)反义寡聚脱氧核苷酸(antisense oligodeoxynucleotides,ASODNs)对增生性视网膜病变视网膜血管发育及新生血管形成的影响.方法注射血管内皮细胞生长因子反义寡聚脱氧核苷酸干预高浓度氧诱导SD幼鼠建立的增殖性视网膜病变动物模型,取眼球作病理切片,计数视网膜新生血管芽、测量视网膜内血管横断面积并比较.结果球后注药组和静脉注药组视网膜新生血管芽细胞核数均明显低于未用药组(P＜0.01);球后注药组与正常对照组比较差异无统计学意义(P＞0.05);而静脉注药组则显著高于正常对照组(P＜0.01).球后注药组(P＜0.01)和静脉注药组(P＜0.05)视网膜内血管横断面积均显著低于正常对照组,球后注药组亦明显低于未用药组(P＜0.05).结论VEGF ASODNs能在明显抑制视网膜新生血管形成的同时,影响新生幼鼠视网膜血管的正常发育,且局部用药作用明显优于全身给药.

Effects of vascular endothelial growth factor antisense oligodeoxynucleotides on the development and neovascularization of retinal vessels in oxygen - induced retinopathy models

OBJECTIVE To assess the effect of VEGF antisense oligodeoxynucleotides(ASODNs) on the development and neovascularization of retinal vessels in oxygen-induced retinopathy.METHODS Oxygen-induced retinopathy models were established by raising the newborn Sprague-Dawley(SD) rats in hyperoxic environment.Retrobulbar injections and caudal vein injections were performed with VEGF ASODNs or normal saline in four groups respectively.The eyeballs were enucleated and fixed by formaldehyde and then cross-sectioned.The nuclei of proliferative retinal vessels were counted and the cross-areas of the retinal vessels were measured.RESULTS The number of the nuclei of the new vessels in retrobulbar injection group and caudal vein injection group were lower than non-disposal group (P<0.01).Compared to normal control group,the nuclei of retrobulbar injection group showed no statistically difference(P>0.05) while caudal vein injection group significantly higher(P<0.01).The cross areas of retinal vessels in both retrobulbar injection group and caudal vein injection group were significantly lower to that of normal control group(P<0.01 and P<0.05 respectively),and that of retrobulbar injection group were also statistically lower than non-disposal group(P<0.05).CONCLUSION VEGF ASODNs can inhibit the retinal neovascularization in the oxygen-induced retinopathy rats as well as interfere the development of normal retinal vessels.The inhibition was more effective when VEGF ASODNs administrated locally than systemically.