土家药白三七抗类风湿性关节炎血管新生作用物质基础及TLR4-NF-κB通路介导的作用机制研究

类风湿性关节炎（RA）是一种自身免疫性疾病，给患者造成了极大的痛苦，但其治疗仍是世界医学界亟待攻破的难题。湘西北土家药白三七具扶正祛邪、祛风除湿、行气止痛之功效，常用于治疗风湿痹症、关节炎等，但其抗RA的药效物质基础和作用机理尚不明确。课题组从白三七中分离到皂苷类成分，尤其是带有罕见人参炔醇基的皂苷类成分，部分成分可抑制血管紧张素II诱导的大鼠血管平滑肌细胞增殖与迁移。前期工作提示白三七皂苷可能通过TLR4-NF-κB通路抑制RA血管新生，减轻关节滑膜炎症而发挥抗RA作用。本课题拟用体外抑制RA成纤维样细胞体内增殖活性为导向，运用现代分离手段分离其中结构新颖的皂苷类成分，利用体外筛选相结合的模式，对白三七总皂苷在TLR4-NF-κB通路中对促炎和促血管生成中起关键作用的基因、蛋白和细胞因子的变化进行研究，阐明白三七RA的药效物质基础和作用机制，为该民族药治疗风湿痹症的应用奠定基础。

As an autoimmune disease, rheumatoid arthritis (RA) has caused great pain to the patients, however, it is still a challenge problem in the world to treat this disease. Tujia ethnomedicine Baisanqi (Panax japonicus C. A. Mey) was recorded to possess the function of expelling wind-evil and removing wetness-evil, regulating “qi” and alleviating pain, make it commonly used in the treatment of wind-dampness, arthralgia-syndrome and various arthritis diseases. However, the therapeutic material basis and mechanism of its anti-RA effect are not clear. In our previous studies, saponins including three polyacetylenic oleanane-type triterpenoids were isolated from Baisanqi, and some of the saponins can inhibit the proliferation and migration of Ang2 induced VSMCs. So the hypothesis was put forward that saponins are the material basis on anti-RA of Baisanqi, and its mechanism may be related to reducing the inflammation of synovium and inhibiting angiogenesis through TLR4-NF-κB pathway. In this study, we aimed to separate the novel saponins guided by the activity of anti proliferation for RA-FLS; the combined screening model of in vitro and in vivo will implement to study the effects of saponins from Baisanqi in alterations of genes, proteins and cytokines which played key roles in pro-angiogenesis and pro-inflammatory in RA, which mediated by TLR4-NF-κB pathway; to clarify the material basis of efficacy and molecular mechanism for Baisanqi in the treatment of RA. This project will provide scientific foundation for the application of this ethnomedicine in treatment of wind-dampness, arthralgia-syndrome, and various arthritis diseases.