Dll4和VEGFR在氧诱导视网膜病小鼠模型中的表达及意义  

Expression of Dll4 and VEGFR with Their Significance in Mice Model of Oxygen-Induced Retinopathy

作　　者：刘王凯[1] 苏毅华[2] 李晓瑜[1] 李易娟[1] 黄越芳[1] 余慕雪[1] 庄思齐[1] 

机构地区：[1]中山大学附属第一医院儿科,广东广州510080 [2]中山大学附属第一医院眼科,广东广州510080

出　　处：《中山大学学报（医学科学版）》2015年第6期857-863,共7页Journal of Sun Yat-Sen University:Medical Sciences

摘　　要：【目的】为了分析Dll4、VEGFR-1、VEGFR-2在视网膜新生血管中的表达,探讨Notch1-Dll4信号通路在氧诱导视网膜病小鼠新生血管形成中的作用。【方法】选用鼠龄7 d的C57BL/6J新生鼠30只,分成实验组和对照组。实验组15只,在氧浓度为(75±2)%的密闭容器中生长5 d,回到室内正常空气中;对照组15只,在室内正常空气中生长。两组各取产后7 d(7 d post-partum,p7)、p12、p17新生鼠5只,摘除眼球,取视网膜提取RNA,以RT-PCR方法检测Dll4、VEGFR-1、VEGFR-2在视网膜中m RNA的表达。【结果】RT-PCR结果显示,在p7和p12时间点时,两组间VEGFR-1表达差异无统计学意义(P>0.05);在p17时间点时,两组间VEGFR-1表达差异有统计学意义(P<0.05),实验组表达量低于对照组;VEGFR-2在各时间位点两组间表达差异无统计学意义(P>0.05);在p7时间点时,两组间Dll4表达差异无统计学意义(P>0.05);在p12和p17时间点时,两组间Dll4表达差异有统计学意义(P<0.05,P<0.05),实验组表达量低于对照组;实验组不同时间点VEGFR-1、Dll4的表达,随着时间的延长而下降(P<0.05,P<0.05);VEGFR-2的表达,随着时间的延长而升高(P<0.05);对照组不同时间点的VEGFR-2表达随着时间延长而增加(P<0.05),而VEGFR-1和Dll4的表达均不随时间变化而变化(P>0.05,P>0.05);Dll4的表达与VEGFR-1的表达呈正相关关系,相关系数r=0.905,P<0.001;而Dll4与VEGFR-2、VEGFR-1与VEGFR-2之间不存在相关关系。【结论】Notch1-Dll4信号通路可能参与了VEGF调控视网膜新生血管生成的过程,Dll4在氧诱导视网膜病小鼠新生血管的形成中表达受到抑制,对VEGF未能进行有效负反馈调控;VEGFR-1的表达受到抑制,且与Dll4表达存在正相关关系;VEGFR-2可能不是视网膜新生血管形成过程中VEGF表达的主要受体。[Objective] To investigate the role that Notchl-Dll4 signal pathway played in the oxygen-induced retinal neovascularization of mice by analyzing the expression of Dl14, 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, 30 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. Five mice were taken from each group at p7（7 d post-partum）, p12, and p17, respectively, and then used the retinas to extract RNA. mRNA expression of Dl14, VEGFR-1 and VEGFR-2 was detected in retinas by RT-PCR. [Results] There was no statistically significant differences in VEGFR-1 expression between these two groups in p7 and p12 （P 〉 0.05）. VEGFR-1 expression of oxygen-induced retinopathy group was lower than the control group （P 〈 0.05）. There was no statistically significant differences in VEGFR-2 expression between these two groups in each timing （P 〉 0.05）. Dl14 expression between the two groups wasnearly the same in p7 （P 〉 0.05）, and the expression of oxygen-induced retinopathy group became lower in p12 and p17 （P 〈 0.05, P 〈 0.05）. As time went on, the expression of VEGFR- 1 and DU4 decreased in each timing （P 〈 0.05, P 〈 0.05 ）, and that of VEGFR-2 increased （P 〈 0.05 ） in oxygen-induced retinopathy group. In control group, the expression of VEGFR-1 and DlI4 protein did not change a lot from p7 to p17 （P 〉 0.05, P 〉 0.05）, and that of VEGFR-2 increased （P 〈 0.05 ）. It showed positive correlation between Dl14 and VEGFR-1,r = 0.905, P 〈0.001. There was no correlativity between Dl14 and VEGFR-2, or between VEGFR-1 and VEGFR-2. [ Conclusion] Notchl - Dl14 signaling pathway may be involved in the regulation of VEGF in the process of retinal angiogenesis. The expression of Dl14 was inhibited in oxygen-induced retinopathy mice during the formation

关 键 词：DLL4 VEGFR 早产儿视网膜病 新生血管 动物模型 

分 类 号：R72[医药卫生—儿科]