基于TNF-α靶点的苗药黑骨藤抗类风湿性关节炎的药效物质基础研究

黑骨藤为贵州省十大苗药之一，常用于类风湿性关节炎（RA）的治疗，已有多个品种上市。课题组对黑骨藤70%醇提物的MCI树脂分段组分进行了系统性研究，发现其抗RA活性与雷公藤多苷片相当，并且能结合TNF-α阻断其生物活性。TNF-α是RA治疗的重要靶点，我们推测黑骨藤能通过靶向结合TNF-α起到抗RA作用。本项目拟将黑骨藤抗RA活性部位进一步细分，并采用细胞模型和报告基因系统来筛选抗TNF-α的活性组分；通过表面等离子共振垂钓技术从活性组分中富集与TNF-α结合的候选活性成分，然后在分子、细胞和动物水平上考察候选成分的抗TNF-α活性，最后通过CIA大鼠和TNF-α转基因小鼠关节炎模型评价其抗RA活性。通过以上研究，将明确黑骨藤中靶向TNF-α的抗RA活性成分，从而完善黑骨藤抗RA的药效物质基础研究，为民族药黑骨藤深层次开发提供科学依据。

Periploca forrestii as one of the top ten Miao drugs in Guizhou province is commonly used for the treatment of rheumatoid arthritis (RA). There are already several varieties into the market. Further studies showed that the fraction subjected to MCI of the 70% ethanol extract could bind to TNF-α and block its biological activity. Meanwhile, its anti-RA activity is as effective as Tripterygium polycoride Tablet. TNF-α is a key target in anti-RA therapy. We hypothesize that Periploca forrestii would exert anti-RA effect by targeting TNF-α. This project is proposed to further subdivide the anti-RA fraction from Periploca forrestii and screen the anti-TNF-α fractions by using cell model and reporter gene system. Surface plasmon resonance technology will be used to enrich candidate active components which can bind TNF-α from the active fractions. The inhibitory effects of the candidate components on TNF-α will be examined with molecule, cell and animal models. Finally, the anti-RA activities of the candidate components will be evaluated by arthritis rat model and TNF-α transgenic mice. Therefore, the anti-RA components targeting TNF-α of Periploca forrestii could be identified to further develop the material basis of its anti-RA activity, which lays a scientific foundation for deep development and application of this ethnic medicine plant.