摘要/Abstract
摘要： 目的 ·研究分化抑制蛋白 -1（inhibitor of differentiation 1，ID1）在眼底新生血管生成过程中的作用。方法 ·建立氧诱导的视网膜新生血管（ OIR）、激光光凝诱导的脉络膜新生血管（ CNV）以及过表达血管内皮生长因子（ vascular endothelial growth factor， VEGF）（Rho-VEGF）转基因小鼠模型。通过免疫荧光染色和实时荧光定量 PCR测定 OIR小鼠模型及 Rho-VEGF转基因小鼠模型视网膜内 ID1的定位及 mRNA含量。采用 ID1基因敲除（ ID1-/-）小鼠，按上述 3种模型诱导视网膜新生血管形成，比较 ID1基因缺失对视网膜、视网膜下及脉络膜新生血管生成面积、数量的影响，探究 ID1在新生血管形成过程中的作用及对相关因子如低氧诱导因子 -1α (hypoxia-inducible factor-1α，HIF-1α)、VEGF以及血管内皮生长因子受体 1/2（vascular endothelial growth factor receptor 1/2， VEGFR1/2）表达的影响。结果 ·在已建立的 OIR小鼠、 Rho-VEGF转基因小鼠和 CNV小鼠这 3种眼底新生血管模型中，与正常对照组相比， ID1-/-小鼠的眼底新生血管面积均显著减小（ P<0.05）。在 ID1-/-小鼠中， HIF-1α、VEGF以及 VEGFR1的表达皆受到抑制。结论 · ID1在缺氧或氧化损伤期间，促进 HIF-1α、VEGF和 VEGFR1的表达，从而促进眼底视网膜和脉络膜新生血管的生成。
关键词: 分化抑制蛋白 -1, 眼底新生血管生成, 低氧诱导因子 -1&, alpha, 血管内皮生长因子, 血管内皮生长因子受体 1
Abstract:
Objective · To study the effect of inhibitor of differentiation 1 (ID1) on ocular neovascularization. Methods · The oxygen-induced retinal neovascularization (OIR), laser-induced choroidal neovascularization (CNV) and over- of vascular endothelial growth factor (VEGF) (Rho-VEGF) transgenic mice were established. The localization and mRNA level of ID1 in retina of OIR mice and Rho-VEGF transgenic mice were determinedimmunofluorescence staining and quantitative real-time PCR. Mice deficient in ID1 (ID1./.) were used to induce retinal neovascularization in accordance with the above three models, and to compare the changes of ID1 on the number of retinal, subretinal and choroidal neovascularization areas. Into explore the role ID1 in neovascularization, the numbers and areas of retinal, subretinal and choroidal neovascularization in the mice models with or without ID1 deficiency were compared. Its effect on the related factors, i.e. hypoxia-inducible factor-1α (HIF-1α), VEGF and vascular endothelial growth factor receptor 1/2 (VEGFR1/2) were also observed. Results · Mice deficient in ID1 showed a significant reduction in the area of neovascularization in these three models(P<0.05). Mice lacking ID1 showed reduced levels of HIF-1α, VEGF and VEGFR 1. Conclusion · ID1 promotes the of HIF-1α, VEGF and VEGFR1 in the retina and choroidal neovascularization during hypoxia and oxidative injury. [Key words]inhibitor of differentiation-1 (ID1); ocular neovascularization; hypoxia-inducible factor-1α (HIF-1α); vascular endothelial growth factor
Key words: inhibitor of differentiation-1 (ID1), ocular neovascularization, hypoxia-inducible factor-1&, alpha, (HIF-1&, alpha, ), vascular endothelial growth factor
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