脂肪组织巨噬细胞（ATMs）替代激活及调控在股骨头坏死发病机制及治疗中的作用研究

项目名称： 脂肪组织巨噬细胞（ATMs）替代激活及调控在股骨头坏死发病机制及治疗中的作用研究

项目编号： No.81201393

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 医学四处

项目作者： 吴星火

作者单位： 华中科技大学

项目金额： 23万元

中文摘要： 激素性骨坏死发病过程中，脂肪分化增强、脂质转运减弱，脂肪细胞异常堆积，激发一系列病理生理反应，导致骨组织缺血坏死。脂肪组织巨噬细胞(ATMs)在骨坏死不同阶段分化成不同功能类型细胞：经典激活巨噬细胞(M1 型)和替代激活巨噬细胞(M2 型)。M1型细胞促进炎症反应进行；M2型细胞抑制炎症反应，促进损伤修复。白介素-4（IL-4）可诱导巨噬细胞替代激活，GM-CSF与IL-4有协同作用。本研究应用IL-4/GM-CSF诱导ATMs替代激活，观察其表型及功能变化特征，尤其是对脂肪细胞增殖、脂质代谢及炎症因子分泌影响，对间充质干细胞成骨成脂分化的影响；通过对骨坏死区M1/M2型ATMs浸润分布及构成比定量分析，探讨ATMs极化差异与骨坏死发生相关性，以及IL-4/GM-CSF替代激活及调控对激素性骨坏死的防治作用；并在此基础上对激素性股骨头坏死发病机理进行深入探讨，寻找骨坏死治疗新的调控靶点。

中文关键词： 骨坏死；巨噬细胞；肿瘤坏死因子；凋亡；白细胞介素-4

英文摘要： Steroid-induced osteonecrosis involves a series of pathophysiological reactions, such as enhanced adipogenesis ,decreased lipid transfer, and accumulated adipocytes, resulting in avascular necrosis of bone tissue. Adipose tissue macrophages (ATMs) are the predominant leukocyte population in fat; during the process of osteonecrosis, ATMs differentiate into different functional types of cells:'Classically activated' M1 macrophages and 'alternatively activated'M2macrophages. M1 ATMs promote the process of inflammation; in contrast, M2 ATMs suppress the inflammatory response and promote enhanced damage repair. Interleukin-4 (IL-4) induces alternative activation of recruited macrophages, and granulocyte macrophage colony stimulating factor (GM-CSF),a common immune adjuvant, has a synergistic effect with IL-4. In the study, the combination of IL-4 and GM-CSF will be used to induce alternative activation of ATMs, then observe the effects on the phenotypic and functional characteristics, especially the effects on adipocyte proliferation, lipid metabolism, inflammatory factor secretion, and the effects on the osteogenic and adipogenic differentiation of mesenchymal stem cells. Through quantitative analysis of the infiltrating distribution and composition of M1 / M2 ATMs in the necrotic area, the relevance between osteon

英文关键词： osteonecrosis；macrophages；TNF-a；apoptosis；IL-4