类风湿关节炎（RA）过度增生的滑膜细胞可能有着类肿瘤细胞生物活性，对DMARDs可产生多药耐药（MDR）,是影响难治性类风湿关节炎（RRA）治疗效果，导致高致残的主要原因之一。我们在国家自然科学基金委员会项目资助下，在国际上较先对RRA患者MDR的形成机制进行了系列研究，初步显示MDR1基因及其编码的P-gp介导的多药耐药是RRA耐药形成的主要机制之一；并初步建立了MDR1/RA滑膜细胞模型及多药耐药的胶原诱导性关节炎大鼠模型。本研究将在前次项目的基础上，从抑制PI3k/Akt/NF-κB通路及MDR1编码的P-gp 着手，运用基因敲除、基因导入、MTT、WB、RT-PCR、基因启动子区缺失分析、染色质免疫沉淀、免疫组织化学、流式细胞分析等技术，从动物、组织、细胞及分子水平探索中药制剂普乐林逆转RRA多药耐药的可能机制，为逆转RRA多药耐药，提高RRA的治疗效果、降低致残率创造新的契机。

There is a similar biological activity between hyperplasia of synoviocytes and unlimited proliferation of tumor cells. Multiple drug resistance (MDR) to DMARDs is the main cause of poor treatment effect in rheumatoid arthritis (RA), leading to high rate of disability. Under the project funded by National Natural Science Foundation of China, we conducted a series of research and became the first team in the world who explored the basic mechanisms of MDR in RRA patients. Our research suggest that MDR1 and P-glycoprotein (P-gp),which is coded by MDR1, plays a key role in the progress of MDR in RRA patients. We have also established MDR1/RA synoviocytes model and MDR CIA rat model, which imitate biological activity in RRA. On the basis of previous studies, we will detect the possibility and mechanisms of peurarin in reversing MDR in RRA at animal, tissue, cell and molecular levels, involving techniques of gene knocking, gene delivery, MTT, WB, RT-PCR, gene promoter deletion analysis, chromatin immunoprecipitation assay and flow cytometry etc. This study aims at reversing MDR and improving treatment effect in RRA.