痛风是以尿酸盐晶体沉积导致关节炎症反应和损伤为特征的一类关节炎，它严重影响人类的身体健康。目前已知巨噬细胞和中性粒细胞在痛风发生发展过程中发挥着重要作用。肥大细胞亦是人体主要免疫细胞之一，其胞内富含大量种类繁多具有较强生物活性的炎症介质，但目前尚未有研究系统观察肥大细胞对痛风发生发展的影响。Rap1b属于Ras激酶家族成员，其可调控免疫细胞的粘附和迁移等功能。我们前期研究结果表明Rap1b-KO可显著促进肥大细胞的活化和脱颗粒。本项目拟通过构建肥大细胞Rap1b-KO小鼠，观察Rap1b-KO肥大细胞对小鼠痛风模型成模的影响。同时研究肥大细胞对中性粒细胞和巨噬细胞功能、软骨基质降解、成纤维样滑膜细胞增殖的影响及其作用机制，重点研究Rap1b在此过程中的调控作用。本项目将明确Rap1b-KO肥大细胞对痛风性关节炎发生发展的影响，并阐明作用机制，为痛风的预防和治疗奠定理论基础和提供潜在的靶标。

Gout is a type of arthritis characterized by inflammation and injury of joints caused by deposition of urate crystals, seriously affecting human health. It is well known that macrophages and neutrophils play an important role in the development of gout. Mast cells are also an important part of immune system, and contain a lot of special cytoplasmic granules which store a large number of inflammatory mediators with strong biological activity. However, presently no systematic studies have been made to observe the effects of mast cells on the initiation and development of gout. Rap1b belongs to Ras kinase superfamily, and plays a critical role in regulating the adhension and migration of immune cells. Our previous studies indicated that Rap1b-KO significantly enhanced mast cell activation and degranulation. This project is going to generate mice with Rap1b-KO mast cells, and observe the influence of Rap1b-KO mast cells on the establishment of mouse model of gout. We will also study the effects of mast cells on the functions of macrophages and neutrophils, degradation of cartilage matrix, the proliferation of fibroblast-like synovial cell and their mechanisms of action, focusing on the regulatory functions of Rap1b. This project will confirm the effects of Rap1b-KO mast cells on the initiation and development of gout, elucidate its mechanisms, laying a theoretical foundation and providing potential targets for the prevention and treatment of gout.