巨噬细胞的极化改变在RA发生和发展中的作用及其调控机制研究

Rheumatoid arthritis is a common autoimmune disease that characterized by synovial inflammation and hyperplasia ("swelling"). As immunocyte, Macrophages play a pivotal role in RA because they involved in development and progression. Recently, Several studies and our preliminary study support Macrophages appear to show various polarized phenotype and function in different stage.But the development,mechanism,impact factor and significance of macrophages polarization in RA have not been fully uncovered. The aim of this study is to test the following research on clinical case and rabbit model of antigen-induced rheumatoid arthritis by flow cytometry , confocal laser scan microscopy, gene arrays and deep sequencing technology：① We would estimate the changes of polarized phenotype,function,CKs and CKR,miR,interferon regulatory factor(IRF) of macrophage in development of RA and regulatory mechanism;②evaluate the significance of change on macrophage polarization in development and progression of RA ;③discuss the influence of miR and IRF on macrophage polarization , in addition on development and progression of RA;④valuation the impact of body immunity and redox state on macrophage polarization ,also on development and progression of RA. It is expected to roundly understand the changes and significance of MΦ in development and progression of RA and deeply comprehend the mechanism of RA.We hope it can provide important theoretical significance for further clarifing the pathogenesis of RA and understanding the rule of occurrence and development of RA.

类风湿性关节炎（RA）是以关节滑膜炎为特征的自身免疫性疾病，巨噬细胞（MΦ）作为一种免疫细胞参与了RA的发生和发展。近期报道及我们的前期研究显示，在RA的不同阶段MΦ可能存在表型和功能的极化改变，但其极化过程的演变、机制、影响因素及意义不明。本课题拟通过临床病例和构建兔RA模型，结合流式细胞术、激光共聚焦、基因芯片和深度测序等技术，系统深入地探讨：①RA进展不同阶段MΦ表型、功能、CKs和CKR表达谱、miR表达谱、干扰素调节因子（IRF）等的改变及其相关机制；②MΦ极化改变对RA进展的意义；③miR和IRF对MΦ极化及RA进展的影响；④机体免疫及氧化还原状态对MΦ极化和RA进展的影响。以期较全面地了解MΦ在RA进展过程中的变化和意义，更深入地理解RA发生和发展的机制，对进一步阐明RA的发病机制、加深对RA发生和发展规律的认识具有重要的理论意义。