Dll4和VEGFR-1,VEGFR-2在氧诱导视网膜病小鼠模型中的关系

发布时间：2018-04-02 04:33

  本文选题：Delta样配体　切入点：血管内皮细胞生长因子受体　出处：《中国儿童保健杂志》2016年08期

【摘要】：目的分析Delta样配体4、血管内皮细胞生长因子受体1、血管内皮细胞生长因子受体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7d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5d,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p7(生后7d)、p12、p17新生鼠5只,摘除眼球,免疫组化法进行Dll4、VEGFR-1、VEGFR-2的测定。结果免疫组化结果显示,对照组和实验组Dll4与VEGFR-1、VEGFR-2在视网膜均可见阳性细胞表达,p7和p12时,两组间VEGFR-1细胞的阳性率差异无统计学意义(P0.05);而在p17时,两组间VEGFR-1细胞的阳性率有差异,实验组低于对照组(P0.05);p7、p12和p17时,两组间VEGFR-2细胞的阳性率差异均无统计学意义(P0.05);p7时,两组间Dll4细胞的阳性率差异无统计学意义(P0.05);而在p12和p17时,两组间Dll4细胞的阳性率差异有统计学意义(P120.05,P170.001),实验组的阳性率低于对照组;实验组不同时间点VEGFR-1和Dll4的阳性细胞率均有降低趋势(P均0.001),VEGFR-2阳性细胞率有增高趋势(P0.05)。对照组不同时间点VEGFR-1的阳性细胞率有降低趋势(P0.05),不同时间点VEGFR-2的阳性细胞率有增高趋势(P0.001),不同时间点Dll4的阳性细胞率没有变化趋势(P0.05)。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表达趋势变化一致。
[Abstract]:Objective to investigate the expression of Delta like ligand 4, vascular endothelial growth factor receptor 1 and vascular endothelial growth factor receptor 2 in retinal neovascularization. To investigate the role of Notch1-Dll4 signaling pathway in angiogenesis of retinopathy mice induced by oxygen, 30 C57BL/6J neonate rats aged 7 days were divided into two groups: experimental group (n = 15) and control group (n = 15). After 5 days of growth in a closed container with oxygen concentration of 75 卤2%, 15 rats in the control group grew in normal indoor air. 5 newborn mice were taken from each group (7 days after birth) and their eyeballs were removed. Immunohistochemical method was used to detect VEGFR-2 in Dll4VEGFR-1 and VEGFR-1VEGFR-2. Results Immunohistochemical results showed that there was no significant difference in the expression of p7 and p12 in Dll4 and VEGFR-1VEGFR-2 in the retina between the two groups, but there was no significant difference in the positive rate of VEGFR-1 cells between the two groups at p17. The positive rate of VEGFR-1 cells in the experimental group was lower than that in the control group (P 0.05, p7p12 and p17). There was no significant difference in the positive rate of VEGFR-2 cells between the two groups. There was no significant difference in the positive rate of Dll4 cells between the two groups at the time of p12 and p17, but at p12 and p17, there was no significant difference in the positive rate of Dll4 cells between the two groups. The positive rate of Dll4 cells in the two groups was significantly higher than that in the control group (P 120.05), and the positive rate in the experimental group was lower than that in the control group. The positive cell rate of VEGFR-1 and Dll4 decreased at different time points in the experimental group. The positive cell rate of VEGFR-2 increased with P 0.001. The positive cell rate of VEGFR-1 decreased at different time points in the control group, and the positive cell rate of VEGFR-2 was decreased at different time points in the control group. The positive cell rate of VEGFR-2 in the control group decreased at different time points, and the positive cell rate of VEGFR-2 at different time points in the control group. The positive cell rate of Dll4 has no change trend at different time points. Conclusion Notch1-Dll4 signaling pathway may be involved in the regulation of retinal angiogenesis by VEGF and Dll4 in oxygen-induced retinopathy mice neovascularization. Its expression is suppressed, The expression of VEGFR-1 was inhibited by negative feedback on VEGF, which was consistent with the trend of Dll4 expression.
【作者单位】： 中山大学附属第一医院儿科;中山大学附属第一医院眼科;
【基金】：2014年广东省公益研究与能力建设专项资金(2014A020212430)
【分类号】：R774.1;R-332

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