基于RA微环境稳态当归补血汤抑制FLS-RA活化效应及分子机制研究

类风湿关节炎（RA）是关节病中研究重点和热点，滑膜过度增生是导致RA发生的病理基础，成纤维细胞样滑膜细胞（FLS-RA）的活化则是滑膜过度增生的病理关键。氧化应激与β-链蛋白(β-catenin)是活化FLS-RA的重要因素，当归补血汤用于RA临床疗效明确，药效组分基本清楚，但其药效物质与其效用靶标及有效组分作用规律尚不清楚。根据已有工作，我们提出假说如下：当归补血汤可能通过抑制FLS-RA活化防治RA，其有效成分阿魏酸通过抗氧化活性抑制FLS-RA活化，黄芪甲苷可以降低滑膜细胞β-catenin表达,二者可能协同抑制FLS-RA活化、重建RA微环境稳态。为此，本研究拟采用在体关节炎大鼠模型和体外培养活化的FLS-RA细胞模型，应用药理学、分子生物学等手段综合评价当归补血汤的抗RA药理作用，阐明其抑制FLS-RA活化的分子机制，揭示当归补血汤的组方配伍科学内涵。

Rheumatoid arthritis (RA) is a research focus and hotspot in arthropathy.Hyperplasia of synovium is the pathological basis in RA.Activation of.Fibroblast-Like Synoviocytes-Rheumatoid Arthritis（FLS-RA）plays important role in these pathological processes.Oxidative stress and β-catenin are important factors for the activation of FLS-RA.Danggui Buxue Decoction is effective for patients of rheumatoid arthritis，and its active components are almost found.However, it is still not clear that the interaction among the active substance and its effective target and effective components.according to the previous work, we put forward the hypothesis: Danggui Buxue Decoction may inhibit FLS-RA activation for controlling RA,The active components of Angelica sinensis (ferulic acid) may inhibit FLS-RA activation by oxidative stress, and the active components of Astragalus membranaceus (astragaloside IV) can down regulate the expression of Wnt/β-catenin signal pathway，According to the prescription compatibility, the combination of the two can inhibit FLS-RA activation，recover RA microenvironment homeostasis.Therefore, we intend to use the culture model of FLS-RA cells activated and Arthritis rat model, Pharmacology and Molecular biological techniques were used,to explore the molecular mechanism of inhibition of FLS-RA activation,and to interpret the scientific meaning and contents of the compatibility of Danggui Buxue Decoction.