基于Notch信号通路调控的益气养阴通痹方干预类风湿关节炎肺间质病变机制研究

类风湿关节炎肺间质病变（RA-ILD）是RA肺部受累主要表现形式，预后差，严重威胁着患者健康，目前对该病的研究较少。研究证实Notch信号通路能诱导成纤维细胞增殖分化，促进细胞外基质（ECM）在肺间质的过度沉积，在肺纤维化形成过程中发挥着关键作用，但目前国内外还没有Notch信号与RA-ILD相关的报道。我们前期曾运用自拟益气养阴通痹方治疗本病取得较为确切的临床疗效，但其作用机制还不清楚。本课题拟运用细胞培养、基因转染、RT-PCR、Western Blot等实验方法，观察在RA-ILD模型大鼠肺成纤维细胞增殖过程中Notch信号通路的作用以及益气养阴通痹方的影响，围绕Notch信号通路探讨该方对RA-ILD模型大鼠肺功能、肺间质病变的干预效应。进一步阐释RA-ILD过程中Notch信号通路的作用，探讨该病发生、发展机制；阐释益气养阴通痹方干预RA-ILD分子机制，为临床应用提供依据。

Rheumatoid arthritis-Interstitial lung disease (RA-ILD) is the main complications of rheumatoid arthritis. The prognosis of the disease is very poor and it easily leads to a serious threat to the health of patients. So far, no much studies about the disease have been conducted. Notch signaling pathways induce excessive deposition of extra cellular matrix (ECM) constitued of collagen in the intersititial parts of lung and eventually leads to pulmonary fibrosis and play an important role in the development of ILD. However,the relation between Notch signaling pathways and RA-ILD was reported. We had made significant effect for the treatment of the RA-ILD disease by yiqiyangyintongbi formula in the past years. However, the mechanisms of yiqiyangyintongbi formula on RA-ILD is unclear. Our research will investigate the effects of Notch signaling pathways on the expression of α-SMA, collagen Ⅰand collagen Ⅲ expression in lung fibroblasts during the development of RA-ILD by some experimental methods, such as cell culture, gene transfection, real time PCR, western Blot, and so on. In addition, we will investigate the effects of yiqiyangyintongbi formula on the lung function and the lung tissue of RA-ILD rat model.By the research, we attempt to reveal the effects of Notch signaling pathways on the development of RA-ILD disease. Meanwhile, we also attempt to reveal the effects of yiqiyangyintongbi formula on the treatment for the RA-ILD disease.