基于TSP1血管新生抑制通路研究丰城鸡血藤黄酮类成分抗RA滑膜血管增生的作用机制及其物质基础

项目名称： 基于TSP1血管新生抑制通路研究丰城鸡血藤黄酮类成分抗RA滑膜血管增生的作用机制及其物质基础

项目编号： No.81460595

项目类型： 地区科学基金项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 张凌

作者单位： 江西中医药大学

项目金额： 49万元

中文摘要： 类风湿性关节炎（RA）是一种以关节滑膜炎为特征的慢性全身自身免疫性疾病，滑膜血管增生是其基本病理特征。鸡血藤是临床治疗RA有确切疗效的中药，但其抗RA的作用机制及活性物质尚未见报道。通过文献与前期研究发现黄酮类成分是鸡血藤主要成分，该类成分与TSP1血管新生抑制通路相关。本课题拟以丰城鸡血藤黄酮类成分为研究对象，以RA滑膜血管增生为切入点，采用胶原诱导性关节炎大鼠模型，研究其抗RA滑膜血管增生的作用机制及调控路径。同时，采用分子印迹技术，研究制备对活性分子有选择性结合位点的聚合物，作为定向分离活性成分材料，在分子水平上对其识别和分离，实现丰城鸡血藤黄酮类单体成分分离纯化富集。再采用体外滑膜血管增生细胞模型，筛选具有抗血管生成活性的单体化合物，并鉴定其化学结构。通过本课题研究，可初步阐明丰城鸡血藤抗RA的药理活性、可能的分子机制以及物质基础，为开发江西道地药材，扩大药源提供科学依据。

中文关键词： 丰城鸡血藤；类风湿关节炎；分子印迹技术；TSP1血管新生抑制通路；黄酮类成分

英文摘要： Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease which relates to joint synovitis，and synovial hyperplasia of blood vessels is the basic pathological characteristics of RA. Millettia has exact curative effect on RA in clinical treatment, but the mechanism of resistance to RA and the related active substances had not been reported yet. By studying on literatures and pre-research we find that flavonoids ingredients are main active substances in Millettia, and these ingredients are related to TSP1 pathway of angiogenesis inhibition. Our subject will focus on the flavonoids of Millettia nitida Benth. var. hirsutissima which is a famous region drug of Jiangxi province, using the RA synovial angiogenesis as the breakthrough point and the rat model of collagen-induced arthritis to study the pharmacological and regulatory path of anti-RA synovial angiogenesis. Meanwhile, research and prepare polymer with selective binding sites of the active molecular in Millettia nitida Benth. var. hirsutissima by molecular imprinting technology as the materials for directional separating active substances. The drugs are recognized and separated from original medicinal in molecular level. By this method, the separation、purify、enrichment of flavonoids and monomeric compounds in Millettia nitida Benth. var. hirsutissima come true. Then we filter monomeric compounds which have anti-angiogenic activity by using synovial angiogenesis cell model in vitro, and identify active substances'chemical structures. Through our research, we will preliminary clarify the anti-RA pharmacological activity、the possible molecular mechanisms and material foundation of Millettia nitida Benth. var. hirsutissima, which can provide scientific references to promote the development of region drug of Jiangxi province and expand medicine source.

英文关键词： Millettia nitida Benth.var.hirsutissima;Rheumatoid Arthritis;Molecular Imprinted technique;TSP1 Pathway of Angiogenesis Inhibition;Flavonoids Compounds