基于SIRT1探讨温针灸调控类风湿性关节炎FLS的机制研究

Rheumatoid arthritis (RA) is characterized by the chronic inflammation and destruction of bone. Fibroblast-like synoviocyte (FLS) plays an important role in these two basic pathological changes. SIRT1 is the common upstream factor of p65 and mTOR, which acts an essential role in inflammatory, immune and bone metabolism, and has a close relationship with the protein of RANKL in FLS. The applicant found in the previous studies that the acupuncture could improve the symptoms of arthritis by inhibiting the expression of p65 protein in synovial tissues of RA rat. In this respect, the project intends to adopt technology of molecular biology and immunology methods, gets RA rat model of type II collagen-induced into use, in order to study the key function of SIRT1 in regulating the function of RANKL of FLS by inhibiting the activation of p65 and mTOR in RA. This project has a great significance on clarifying the molecular mechanisms of warm acu-moxibustion in treatment of RA. Furthermore, it will facilitate the discovery of new and relevant processes and new targets for therapy in RA.

类风湿性关节炎(RA)其特征性的病理改变是滑膜慢性炎症和骨质破坏。成纤维样滑膜细胞(FLS)在这两个基本病理改变中均起到重要作用。SIRT1作为p65与mTOR上游因子，在炎症、免疫及骨代谢中起重要的侨联作用，并且与FLS中的RANKL基因存在着密切联系。申请人在前期实验中发现，针灸可以通过抑制RA滑膜组织中p65表达改善RA大鼠关节炎症状。为此本项目拟采用分子生物学和免疫学技术，以II 型胶原诱导的RA大鼠为模型，SIRT1为中心控点，可能通过影响p65/mTOR来调控FLS和RANKL基因。以期阐明温针灸治疗RA的分子机制和作用靶点，为临床运用针刺防治RA及其相关性疾病提供全新的科学依据，有望为RA的治疗提供一条新思路。

类风湿性关节炎(RA)其特征性的病理改变是滑膜慢性炎症和骨质破坏。成纤维样滑膜细胞 (FLS)在这两个基本病理改变中均起到重要作用。SIRT1作为p65与mTOR上游因子，在炎症、免疫及骨代谢中起重要的侨联作用，并且与FLS中的RANKL基因存在着密切联系。本实验研究发现，针灸可以通过抑制RA滑膜组织中p65表达改善RA大鼠关节炎症状，通过调节软骨细胞骨架蛋白Vimentin、滑膜组织ICAM-1、VCAM-1，对骨关节炎症白介素类炎症因子和抑炎因子有较好的调节作用。