靶向调控SDF-1/CXCR4信号通路干预关节软骨退变的分子机理研究

项目名称： 靶向调控SDF-1/CXCR4信号通路干预关节软骨退变的分子机理研究

项目编号： No.81460340

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： 李彦林

作者单位： 昆明医科大学

项目金额： 47万元

中文摘要： 随着社会人口的老龄化，以关节软骨退变为特征的OA患病率日益剧增，而靶向SDF-1/CXCR4信号通路可调控关节软骨退变，本研究用高效稳定的拮抗剂TN14003阻断SDF-1/CXCR4信号通路，并与T140及AMD3100对照，从分子、细胞、组织及体内水平调控OA软骨退变，用光亲和标记技术探讨各拮抗剂的分子作用机理，观察其阻断SDF-1/CXCR4信号通路对OA软骨细胞的生物学效应，经组织学观察、ELISA测定、RT-PCR和Western blot检测OA患者软骨组织体外降解情况。在此基础上，用Alzet微量泵于原发性OA豚鼠体内予靶向药物TN14003、T140及AMD3100，探讨其体内调控OA软骨退变的作用， 经组织学观察，免疫组化染色，ELISA测定，RT-PCR及Western blot检测，探寻阻止OA软骨病理进程新的靶向药物，为研发高效安全的OA靶向药物提供实验依据。

中文关键词： T140类似物；SDF-1/CXCR4信号通路；靶向治疗；骨性关节炎；软骨退变

英文摘要： As the population ages,the prevalence rate of osteoarthritis (OA)distinguished by cartilage degeneration increases daily, and targeting for SDF-1/CXCR4 signaling pathway could regulate articular cartilage degeneration, so in this study,the high effective and biological stable T140 analog TN14003 is used to block SDF-1 / CXCR4 signaling pathway,T140 and AMD3100 are used as control study.The OA cartilage degeneration will be regulated through molecular,cellular, tissue level and in vivo.The molecular mechanism of the antagonists is investigated with photoaffinity labeling, and the biological effect of OA chondrocytes is observed after blocking SDF-1 / CXCR4 signaling pathway. The histological observation, ELISA assay, RT-PCR and Western blot are used to observe the cartilage tissue degradation of OA patients in vitro. On this basis,TN14003,T140 and AMD3100 are administered with Alzet pump in Hartley guinea pig animal model with primary OA to block SDF-1/CXCR4 signaling pathway and explore the regulation the degeneration of OA cartilage tissue in vivo.The both knee cartilage tissue are collected and observed with histological observation, immunohistochemical staining, ELISA assay, RT-PCR and Western blot.The aim is to explore the new high effective medicine targeting for SDF-1 / CXCR4 signaling pathway and prevent the degenerative pathological process of OA cartilage, it could provide the experimental basis and explore the clinical high effective and safe targeting drugs for OA.

英文关键词： T140 analog;SDF-1/CXCR4 signaling pathway;targeting therapy;osteoarthritis;cartilage degeneration