类风湿性关节炎（RA）可导致不可逆的关节畸形，给患者带来严重的痛苦。本课题组前期研究发现淋巴系统与RA发病紧密相关，RA慢性炎症造成淋巴管内皮细胞（LECs）表达iNOS，产生一氧化氮（NO），损伤集合淋巴管平滑肌细胞（LSMCs）的结构和功能，导致淋巴回流障碍，加重关节炎症。但炎症因子诱导LECs表达iNOS的信号通路分子机制并不清楚。《医学心悟》之蠲痹汤是中医治疗RA的常用方剂，前期研究发现其改善RA小鼠关节炎症，促进淋巴回流，减轻炎症诱导LECs表达iNOS和NO, 但药理机制仍需深入研究。本项目以TNF-Tg RA小鼠模型和体外培养LECs为研究对象，研究炎症因子TNFα诱导LECs表达iNOS的分子机制及蠲痹汤调控LECs的TNFα/iNOS/NO信号通路，减少NO损伤LSMCs，改善淋巴回流功能，减轻RA的药理机制。

Rheumatoid arthritis (RA) can lead to irreversible joint deformity, causing serious pain to patients. Previously, we found that lymphatic system plays an important role in RA, inflammatory cytokines stimulate lymphatic endothelial cells (LECs) express iNOS and produce nitric oxide (NO) to damage the structure and function of smooth muscle cells (LSMCs) at collect lymphatic vessels, lead to dysfunction of lymphatic drainage, and aggravate arthritis. But the molecular mechanism of iNOS expression of LECs induced by TNFα is not clear. Juanbi Tang of is commonly used as traditional Chinese medicine for the treatment of RA. Our previous studies suggested that Juanbi Tang could attenuate joint inflammation and promote lymphatic drainage in a mouse model of RA, and reduce iNOS expression and NO production of LECs induced by TNFα. But the mechanisms need further study. The aim of current project is to apply TNF-Tg RA mouse models and in vitro culture of LECs to research the molecular mechanisms of TNFα induced iNOS expression of LECs and Juanbi Tang block TNFα/iNOS/NO signaling pathway of LECs to reduce the impairment of LSMCs, improve the lymphatic drainage function, and alleviate the inflammation severity of RA.