威灵仙为治痹之要药，治疗风湿骨痹药专力宏，历代医家倍加推崇，目前研究疏于对其药效物质协同起效治疗“骨”之病变的探索。本课题依据传统中医对风湿骨痹病机的论断，基于申请人前期获得国家自然科学基金青年科学基金资助81503234，立足于前期研究发现的威灵仙不同药效部位和化合物可抑制软骨细胞凋亡和基质金属蛋白酶，以抑制骨关节炎(OA)软骨退行性病变为切入点，采用中药药效物质“显效理论”，提出假说：治痹要药威灵仙，其“显效形式”在同一靶点和不同靶点以叠加和协同的作用方式，通过抗细胞外基质降解和软骨细胞凋亡，达到治疗OA软骨退行性病变之目的。本课题首先通过LC-MS导向分离和体内代谢研究阐明威灵仙的显效物质基础，进一步从整体、组织、细胞、信号通路四个层面研究其对细胞外基质降解和软骨细胞凋亡的作用途径，探讨其显效形式在作用靶点上的叠加和协同作用，以揭示威灵仙治疗风湿骨痹的物质基础及多靶点协同作用机制。

Radix and rhizoma clematidis are the most important and effective traditional Chinese medicine (TCM) to treat “Bi-Syndrome” (osteoarthritis OA), and it is widely used in ancient and modern prescriptions. However, curative effect on cartilage degeneration exerted by wholly effective substances have not been satisfactorily examined.. According to the TCM comprehension on Bi-Syndrome and with the financial support of NSFC (81503234), we found that certain extraction and effective compounds showed inhibition activities against matrix metalloproteinase and chondrocyte apoptosis.. So, taking curative effect on cartilage degeneration as breakthrough and “effective form theory” as guidance, we hypothesis that the curative effect on OA cartilage degeneration of radix and rhizoma clematidis is realized by effective substances acting upon the single target in additive way, and upon different targets in synergistic way, to exert inhibition activities against extracellular matrix degradation and chondrocyte apoptosis.. In the research, we explore the effective substances of radix and rhizoma clematidis by LC-MS guided isolation and metabolism investigations, further screen those effective substances by extracellular matrix degradation and chondrocyte apoptosis experiments in vitro. For vivo study, effects on related animal physiology, tissue lesions, cytokine and gene expression will be evaluated. At last, the additive and synergistic ways of effective substances will be investigated, to uncover the effective substances and synergistic mechanism on OA cartilage degeneration of radix and rhizoma clematidis.