类风湿关节炎（RA）是一种严重危害人类健康的自身免疫病，致残率高，机制不详。RA滑膜组织新生血管形成可加剧滑膜炎症反应，导致关节软骨和骨破坏，成为RA发生发展的重要病理基础，然而迄今尚未找到防治滑膜血管新生的最佳作用靶点。1-磷酸鞘氨醇（S1P）是肿瘤和炎症反应中关键的促血管生成分子，在RA关节中表达增加，但具体作用尚不明确。我们在前期工作中发现S1P可诱导RA滑膜成纤维细胞分泌白细胞介素-6，后者是RA滑膜中重要的促血管生成因子，因此我们推测S1P是RA血管新生的诱导剂。为证明该假说，本研究拟在分子、细胞和整体动物水平上研究S1P与滑膜血管新生的关系，通过干扰其激酶-受体途径，探讨关键作用靶点，并通过复制细胞炎症模型和缺氧模型，模拟RA关节腔内环境，探讨S1P途径的信号转导机制，从而为进一步探索RA发病机制奠定理论基础，为寻找新的靶向治疗药物提供实验依据。

Rheumatoid arthritis (RA) is an autoimmune disease which seriously jeopardizes human health. It is a common cause of disability with unclear etiology. Angiogenesis is an important pathological basis of RA, which exacerbates synovitis, leading to the destruction of articular cartilage and bone. However, the optimized target for angiogenesis has not been found yet. Sphingosine-1-phosphate (S1P) has been emerged as a mediator of angiogenesis both in tumor growth and inflammation. S1P is highly expressed in RA synovium, but its role in RA is not clear. In the previous work, we found that S1P-induced RA synovial fibroblasts secreted high level of interleukin-6, which is an important angiogenic factor in RA synovium. We therefore speculate that S1P is an inducer of RA angiogenesis. This project intends to clarify the role of S1P in RA synovial angiogenesis in order to prove this hypothesis. Research on molecular, cellular and whole animal levels will be performed to represent the mechanisms involved in this process. Both animal and cell models of RA as well as angiogenesis model will be utilized to locate the critical target for S1P-S1P receptor signaling system. Our research aims to provide theoretical basis and seek new target point for RA treatment.