从Treg与HMGB1-RAGE/RANKL-RANK探讨益肾蠲痹丸治疗RA继发OP的骨免疫机制

The rheumatoid arthritis secondary osteoporosis shows high incidence, which serious affect the quality of life of RA patients, and its pathogenesis has not been elucidated. Regulatory T cells (Treg) modulate the immune system by the passage of RANKL-RANK homeostatic inhibit osteoclast (OC) proliferation. HMGB1-RAGE can enhancing the passage to promote the proliferation of OC effect and inhibiting Treg function. Therefore, Treg/HMGB1-RAGE/RANKL-RANK interacts with each other in the process of the occurrence of osteoporosis. Preliminary studies confirmed that the animal models of RA exists a high expression of HMGB1-RAGE. This project intends to study the interconnection of Treg/HMGB1-RAGE from the whole, tissue and cellular level, and explore the bone immune mechanism of yi shen juan bi pill on RA secondary OP, based on Treg/HMGB1-RAGE pathway to bone destruction and yi shen juan bi pill as a tool for drug, combined with the classic model of arthritis, bone morphogenetic the stoichiometry, micro CT scan, flow cytometry and RT-PCR method, in order to provide the scientific data for the arthralgia bone immune mechanism and provides a new target for drug treatment of RA.

类风湿关节炎（RA）继发性骨质疏松（OP）发病率高，严重影响患者生活质量，其发病机制尚不明确。调节性T细胞（Treg）能够通过RANKL-RANK通路调节免疫系统自身平衡，抑制破骨细胞(OC)增殖，相反HMGB1-RAGE能够增强RANKL-RANK通路促OC增殖效应，抑制Treg功能，因此Treg/HMGB1-RAGE/RANKL-RANK三者在骨质疏松的发生过程中存在相互作用。前期研究证实RA动物模型存在HMGB1-RAGE的高表达，本项目拟基于Treg/HMGB1-RAGE通路，以具有骨破坏修复作用的益肾蠲痹丸为工具药，结合经典关节炎模型，采用骨形态学计量、micro CT扫描、流式细胞分析及RT-PCR等方法，从整体、组织及细胞水平深入研究Treg/HMGB1-RAGE的相互关联，探讨益肾蠲痹丸治疗RA继发OP的骨免疫机制，为中医痹症骨免疫机制研究提供科学数据及药物治疗RA的新靶标

类风湿关节炎（RA）继发性骨质疏松（OP）发病率高，严重影响患者生活质量，其发病机制尚不明确。调节性T 细胞（Tregs）能够通过RANKL-RANK 通路调节免疫系统自身平衡，抑制破骨细胞(OC)增殖，相反HMGB1-RAGE 能够增强RANKL-RANK 通路促OC 增殖效应，抑制Tregs 功能。本研究通过整体实验证实益肾蠲痹丸(YSJB)能够减轻CIA骨破坏严重程度，对淋巴组织中T淋巴细胞亚群有调节作用，提示YSJB可能通过调节免疫状态，增强免疫抑制功能而发挥对RA的治疗作用。体外实验选择OC-Tregs比例为50：2构建成功OC-Tregs共培养体系，发现Tregs分泌的IL-10在促进OC分化中具有重要作用。YSJB含药血清可以通过调节Treg促进HMGB1-RAGE/RANKL-RANK介导的OC分化。体外和体内实验相结合，证实补肾通络方药YSJB通过调节Treg和HMGB1-RAGE/RANKL-RANK介导的OC分化的骨免疫机制，为丰富中医药治疗痹证提供科学依据。