白细胞介素-10调控巨噬细胞以促进眼底新生血管形成  

IL-10 promotes ocular neovascularization by regulating macrophages

作　　者：隋爱玲[1] 苏婷[1] 高誉硕 朱艳吉[1] 谢冰[1] SUI Ai-ling SU Ting GAO Yu-shuo ZHU Yan-ji XIE Bing(Department of Ophthalmology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, Chin)

机构地区：[1]上海交通大学医学院附属瑞金医院眼科,上海200025

出　　处：《上海交通大学学报（医学版）》2017年第3期278-287,共10页Journal of Shanghai Jiao tong University:Medical Science

基　　金：国家自然科学基金(81570853)~~

摘　　要：目的·研究白细胞介素-10(IL-10)对眼底新生血管(NV)的影响。方法·采用免疫荧光、RT-PCR、Western blotting等方法检测在氧诱导视网膜病变(OIR)小鼠模型及VEGF过表达(rho/VEGF)转基因小鼠模型中IL-10的表达。应用IL-10基因敲除鼠,研究IL-10对视网膜、视网膜下及脉络膜新生血管的影响。结果·在OIR及rho/VEGF转基因小鼠模型中,IL-10的免疫荧光染色强度增加,IL-10的m RNA表达量也升高。与正常对照组小鼠相比,IL-10基因敲除鼠(IL-10-/-)由OIR诱导的新生血管和激光诱导脉络膜新生血管(CNV)均显著减少。并且,在IL-10基因敲除鼠中,其低氧诱导因子-1α(HIF-1α)以及血管内皮生长因子(VEGF)和血管内皮生长因子受体1(VEGFR1)的表达均减少。在IL-10基因敲除的OIR小鼠模型视网膜中,巨噬细胞受调控后数量减少。结论·IL-10通过刺激HIF-1α及VEGF、VEGFR1的表达而促进眼新生血管的形成。IL-10在视网膜缺氧时通过调控巨噬细胞,促进眼新生血管的形成。Objective · To investigate the role of interleukin-10 （IL-10） in regulating ocular neovascularization （NV）. Methods · Expression of IL-10 was investigated in mice with oxygen-induced retinopathy （OIR） and transgenic mice with VEGF expression in photoreceptors by immunofluorescence, RT-PCR, and Western blotting. Mice deficient in IL-10 were used to test the effect of IL-10 in retinal, sub-retinal, and choroidal NV. Results · In OIR mice and transgenic mice with VEGF expression in photoreceptors, the staining intensity and mRNA expression of IL-10 were increased. Mice deficient in IL-10 showed a significant reduction in ischemia-induced retinal NV, and choroidal NV at rupture sites in Bruch’s membrane. Mice lacking IL-10 showed reduced levels of hypoxia-inducible factor-1α （HIF-1α） and suppression of ischemia-induced expression of VEGF and VEGF receptor 1. Macrophage was regulated and reduced in ischemic retina of mice with IL-10 deficiency. Conclusion · IL-10 stimulates ocular NV through modulation of HIF-1α and its target genes VEGF and VEGF receptor 1. IL-10 promotes ocular NV via macrophage response to retina ischemia.

关 键 词：白细胞介素-10 巨噬细胞 低氧诱导因子-1Α 血管内皮生长因子 

分 类 号：R77[医药卫生—眼科]