基于Notch信号途径和Treg /Thl7平衡变化对系统性红斑狼疮肺间质病变模型鼠的影响及雷公藤多甙干预机制研究

肺间质病变（ILD）是SLE肺部受累主要表现形式，预后差，严重威胁着患者健康。研究证实Notch信号通路能诱导成纤维细胞增殖，促进细胞外基质在肺间质的过度沉积，在ILD形成中发挥着关键作用；Th17/Treg平衡与SLE的发病存在显著关联。目前国内外还没有Notch信号通路、Th17/Treg平衡变化与SLE-ILD相关的报道。我们曾运用雷公藤多甙治疗RA-ILD取得较为确切的临床疗效，该药具有抑制纤维增生、抗炎、抑制免疫等作用。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SLE-ILD模型鼠肺成纤维细胞增殖过程中Notch信号通路和Th17/Treg平衡的作用及雷公藤多甙的影响，围绕Notch信号通路和Th17/Treg平衡变化探讨该药对SLE-ILD模型鼠肺功能、肺间质病变的干预效应，进一步阐释SLE-ILD发病机制和雷公藤多甙的干预机制。

Systemic lupus erythematosus-Interstitial lung disease(SLE-ILD) is the main complications of systemic lupus erythematosus. The prognosis of the disease is 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.The Th17/Treg balance was also associated with the incidence of SLE and ILD.However,the relation between Notch signaling pathways,Th17/Treg balance and SLE-ILD were not reported. We had made significant effect for the treatment of the RA-ILD disease by tripterygium glycosides in the past years.Tripterygium glycosides has the effect of inhibiting the proliferation, anti-inflammatory and immunosuppression of the fibers.Our research will investigate the effects of Notch signaling pathways and Th17/Treg balance on the expression of α-SMA, collagen Ⅰand collagen Ⅲ expression in lung fibroblasts during the development of SLE-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 tripterygium glycosides on the lung function and the lung tissue of SLE-ILD rat model.By the research, we attempt to reveal the effects of Notch signaling pathways and Th17/Treg balance on the development of SLE-ILD disease.Meanwhile, we also attempt to reveal the effects of tripterygium glycosides on the treatment for the SLE-ILD disease.