补肾活血汤干预瘦素调控骨关节炎软骨、滑膜及脂肪细胞交互作用的网络机制研究

项目名称： 补肾活血汤干预瘦素调控骨关节炎软骨、滑膜及脂肪细胞交互作用的网络机制研究

项目编号： No.81473710

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 魏民

作者单位： 中国人民解放军总医院

项目金额： 74万元

中文摘要： 骨关节炎（OA）是严重危害人类健康的慢性骨关节疾病，中药治疗OA有悠久历史和独特优势，并已取得良好临床疗效。我课题组在前期研究中证实中药方剂补肾活血汤能有效改善OA临床症状，具显著疗效。依据相关动物实验文献，补肾活血汤能改善OA局部微循环，调节理化环境，延缓软骨退变，但作用机制尚待揭示。新近研究发现除IL-1、TGF-β等经典炎症相关因子外，脂肪因子瘦素特异性地以显著高于血循环的浓度在OA局部高表达，参与OA病理过程，有可能成为OA治疗靶分子。在多囊卵巢实验大鼠模型中已证实补肾活血方能调控机体脂肪代谢并下调瘦素表达；但其对骨关节微环境的调控作用未见研究。本申请拟以软骨、滑膜及脂肪细胞交互作用网络为研究对象，通过组学、系统生物学大规模数据分析及分子生物学技术研究补肾活血汤干预OA的分子机制。课题完成不仅能为临床用药提供科学依据，还将推进对OA发生发展机制的认识，促进临床辩证论治。

中文关键词： 骨关节炎；补肾活血汤；瘦素

英文摘要： Osteoarthritis (OA), as the most common form of arthritis, is a disease with formidable impact on human healthy. Traditional Chinese medicine treatment for OA has long history, and has distinct characteristics and advantages. We have identified that Bushen Huoxue decoction had significant clinical efficiency in OA therapy. It has been verified by experimental studies in rat and rabbit model that Bushen Huoxue decoction delayed joint cartilage degeneration by improving micro-circulation and regulating the intra-articular micro-environment, while the molecular mechanism was unclear. Recent studies indicated that leptin may be one of the central adipokine mediators being investigated for metabolic-osteoarthritis link. In addition to classic pro-inflammatory factors, such as IL-1 and TGF-β, Leptin over-expressed in local joint of OA patients specifically, and contributed to OA pathobiology. Leptin is unique among other adipokines analyzed to date in that only leptin has been found to exist at higher concentrations in the synovial fluid compared to serum. These facts pointed out that Leptin may be new biomarkers or molecular targets in OA diagnosis and therapy. It has been reported that Bushen Huoxue decoction could effectively reduce serum leptin level in polycystic ovary syndrome (PCOS) rat model, while the function of this Chinese herbal involved in articular micro-environment regulation was unknown. In this study, we would continue to identify the expression pattern of a set of OA-associated cytokines, proteases, and adipokines before and after Bushen Huoxue decoction treatment to assess the molecular mechanism of Bushen Huoxue decoction in OA therapy by using proteomic, genomic and systems biology approaches, and analyze the Bushen Huoxue decoction-inducd cellular responses and the cross-talk networks of OA articular cells, including cartilage, synovial and lipocytes. The results of this study will construct the OA-associated cytokins, proteases and adipokines data pool, provide theories for clinical application of Bushen Huoxue decoction, and will be helpful for our understanding of the onset and the progression of OA.

英文关键词： Osteoarthritis (OA);Bushen Huoxue Decoction;leptin