Objective To investigate the role that Notch1-Dll4 signal pathway played in the oxygen-induced retinal neovascularization of mice by analyzing the expression of Dll4,VEGFR-1,and VEGFR-2 in retinal neovascularization. Methods Thirty 7-day-old C57BL/6J mice were divided into oxygen-induced retinopathy group and control group.In oxygen-induced retinopathy group,15 mice were exposed to (75±2) % oxygen for 5 days and then back to room air.In control group,15 mice were raised in room air.5 mice were taken from each group at p7(postnatal seventh day),p12 and p17 respectively,and then enucleated the eyeballs to detect the Dll4,VEGFR-1 and VEGFR-2 by immunohistochemistry. Results There were Dll4,VEGFR-1 and VEGFR-2 positive cells in the retina of both groups.The positive rate of VEGFR-1 had no difference between two groups in p7 and p12 (P＞0.05).While in p17,the positive rate of VEGFR-1 in oxygen-induced retinopathy group was lower than that in control group(P<0.05).The positive rate of VEGFR-2 had no difference between two groups in p7,p12,p17(P＞0.05).The positive rate of Dll4 had of no difference between these two groups in p7(P＞0.05),and in p12 and p17,the positive rate of Dll4 in oxygen-induced retinopathy group was lower than that in control group (P12＜0.05,P17＜0.001).In oxygen-induced retinopathy group,the positive rate of VEGFR-1 and Dll4 decreased from p7 to p17(P＜0.001,P＜0.001),and that of VEGFR-2 increased from p7 to p17 (P＜0.05).In control group,the positive rate of VEGFR-1 showed a decreased tendency at different timing(P＜0.05=0.017),and that of VEGFR-2 increased at different timing(P＜0.001),while that of Dll4 didn't changed obviously(P＞0.05). Conclusion Notch1 - Dll4 signaling pathway may be involved in the regulation of VEGF in the process of retinal angiogenesis.The expression of Dll4 is inhibited in oxygen-induced retinopathy mice during the formation of neovascularization,so it failed to show negative feedback regulation to VEGF; The expression of VEGFR-1 is inhibited in oxygen-induced retinopathy mice and has a consistent trend with Dll4.
Key words
delta-like ligand 4 /
vascular endothelial growth factor /
retinopathy of prematurity:neovascularization /
animal model
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