Shp2调控巨噬细胞极化参与痛风性关节炎的机制研究

痛风性关节炎是由长期血尿酸升高产生尿酸盐结晶沉积导致的急、慢性炎症性损伤，常具有自限性。巨噬细胞是痛风发生发展过程中的重要免疫细胞之一，前期研究发现部分巨噬细胞在疾病早期即向M2极化，参与炎症缓解过程，而该极化过程受去乙酰化酶Sirt1的调控，但具体机制不明。近年研究报道酪氨酸磷酸酶（Shp2）可能影响巨噬细胞极化。因此，本课题拟观察Shp2在痛风性关节炎自愈过程中的效应并对其具体机制进行深入探讨。首先，明确Shp2在痛风中的变化及其对巨噬细胞极化的调控作用；其次，探讨线粒体转位蛋白（TSPO）复合物对Shp2的胞内转运作用及其对线粒体能量代谢的影响，阐明Shp2调节巨噬细胞极化的机制；最后，验证Sirt1对Shp2表达、转运以及上述巨噬细胞极化机制的调控作用。希望通过本研究，对Shp2在痛风中的作用及其对巨噬细胞极化的调控有深入的认识，为痛风的防治提供新的视角。

Gout is a type of inflammatory arthritis due to excess monosodium urate crystals depostition . Acute attack of gout often shows self-limiting, but the mechanism has not been known so far. Macrophages are one of the important immune cells which effect on the development of gout. Our previous research found that macrophages polarized to M2 in the early stage of the disease and participated in the process of inflammation relief were regulated by Sirt1. Recent studies reported that tyrosine phosphatase (Shp2) might affect macrophage polarization. Therefore, this project aims to observe the effect of Shp2 in the self-limiting process of gout and to explore its specific mechanism. Firstly, we clarified the changes of Shp2 in gout and its regulation of macrophage polarization. Then, we explored the intracellular transport of Shp2 by mitochondrial translocation protein (TSPO) complex and its effect on mitochondrial energy metabolism. Finally, we verified the regulatory effect of Sirt1 on this mechanism to provide new research targets for the prevention and treatment of gout. In this study, we explore an impressive understanding of the role of Shp2 in gout, the regulatory effect of Shp2 and the polarization of macrophages. This study may provide a new perspective on the prevention and treatment of gout.