上海交通大学学报（医学版）

上海交通大学学报（医学版）

• 论著（基础研究） • 上一篇    下一篇

白细胞介素-10调控巨噬细胞以促进眼底新生血管形成

隋爱玲，苏婷，高誉硕，朱艳吉，谢冰   

  1. 上海交通大学 医学院附属瑞金医院眼科，上海 200025
  • 出版日期:2017-03-28 发布日期:2017-03-30
  • 通讯作者: 谢冰，电子信箱：brinkleybing@126.com。
  • 作者简介:隋爱玲（1990—），女，硕士生；电子信箱：ailingsui@163.com。
  • 基金资助:

    国家自然科学基金（81570853）

IL-10 promotes ocular neovascularization by regulating macrophages

SUI Ai-ling, SU Ting, GAO Yu-shuo, ZHU Yan-ji, XIE Bing   

  1. Department of Ophthalmology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
  • Online:2017-03-28 Published:2017-03-30
  • Supported by:

    National Natural Science Foundation of China，81570853

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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mRNA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。

关键词: 白细胞介素-10；巨噬细胞；低氧诱导因子-1&alpha, ；血管内皮生长因子

Abstract:

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.

Key words: interleukin-10, macrophage, hypoxia-inducible factor-1α, vascular endothelial growth factor