Notch信号通路调控巨噬细胞参与脉络膜新生血管生成的作用、机制和干预

项目名称： Notch信号通路调控巨噬细胞参与脉络膜新生血管生成的作用、机制和干预

项目编号： No.81200707

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 医学二处

项目作者： 窦国睿

作者单位： 中国人民解放军第四军医大学

项目金额： 23万元

中文摘要： 巨噬细胞作为重要的炎症细胞，参与多种致盲眼病的共同病理基础-脉络膜新生血管（CNV）的生成。但在CNV中巨噬细胞是如何被激活和极化，对新生血管生成有何影响，及相关调控机制等问题目前尚不清楚。我们既往首次报道Notch信号在CNV发生发展中具有负性调控作用，并在近期工作中发现Notch信号参与调控巨噬细胞的M1/M2极化反应从而影响血管新生，提示Notch信号可能通过调控巨噬细胞参与CNV生成。本课题拟在此基础上，利用巨噬细胞中特异性Notch信号缺失和激活的转基因小鼠，结合激光诱导小鼠CNV模型，通过体内和体外实验，研究Notch信号通过调控巨噬细胞参与CNV生成；揭示Notch调控下不同极化形式的巨噬细胞对CNV的影响和机制；探讨巨噬细胞中Notch信号对CNV潜在的治疗价值。这将有助于深入了解CNV生成中炎症细胞的分子调控机理，对在此基础上开发CNV靶向药物，具有重要的理论和实际意义。

中文关键词： Notch信号；脉络膜新生血管；巨噬细胞；血管生成；极化

英文摘要： Macrophages have been recognized as the important inflammatory components which participate in choroidal neovascularization (CNV). However, it is unclear till now that how these cells are activated and polarized; how they affect angiogenesis and what are the underlining mechanisms. Based on our previous study that Notch signaling pathway plays a negative role in the development of CNV, and a recent finding that Notch signaling could direct the polarization of macrophage, it is intriguing to hypothesize that Notch regulates macrophage in the formation of CNV. By using the myeloid specific Notch signaling deletion or activation transgenic mice model with laser-induced CNV model, the current study aims to investigate how Notch signaling regulates macrophage in CNV; to unveil the mechanisms of polarized macrophage regulated by Notch in CNV development; to explore the potential therapeutic strategies of Notch signaling for CNV-related disease. These findings would offer theoretical reflections on the molecular mechanism of inflammation in CNV and the development of therapeutic target to CNV, as well as a deeper understanding on Notch signaling.

英文关键词： Notch signal；choroidal neovascularization；macrophage；angiogenesis；polarization