中文摘要：

目的观察类风湿关节炎（RA）滑液中存在的大量细胞亲环素A（CypA）是否可以上调RA滑液中细胞膜表面高表达CD147分子的单核／巨噬细胞基质金属蛋白酶（MMP）-2和MMP-9的表达及活性，并确定这一调节是否需要CDl47分子信号通路的参与。方法重组人CyPA（200ng／mL）刺激人单核细胞系THP-l细胞24h。进行实时定量RT-PCR及明胶酶谱分析MMP-2和MMP-9mRNA表达及酶活性的改变：加入抗CDl47拮抗肽AP-9阻断细胞膜分子CDl47的作用。临床收集10例确诊的活动期RA患者外周血及关节腔滑液，分离获得单核／巨噬细胞，观察CypA对其MMP-2和MMP-9表达的影响。结果CyPA增加分化前及分化后THP-1细胞MMP-9 mRNA及蛋白的表达和活性，而对MMP-2则无作用；环孢素A（CsA）及抗CDl47拮抗肽AP-9显著抑制THP-1细胞MMP-2和MMP-9 mRNA表达及其分泌和活性及阻断CypA的上调作用。CyPA对RA关节腔滑液内单核／巨噬细胞MMP-9的表达和活性具有促进作用。结论CypA通过CD147受体的参与，上调RA关节腔滑液内单核／巨噬细胞MMP-9的表达及其活性，这一作用机制为RA发病机制及其治疗提供了新的理论基础。

英文摘要：

Objective Cyclophilin A （CypA） is abundant in rheumatoid arthritis （RA） synovial fluid.CD 147, the receptor of CypA, is highly expressed on the monocytes/macrophages cells of RA synovial fluid and synovium. To determine whether CypA can upregulate the expression of matrix metalloproteinase （MMP）-2 and MMP-9 in monocytes/macrophages and whether CD147 facilitates this regulation. Methods Human monocyte cell line, THP-1 cells, were stimulated with CypA, the levels of MMP-2 and MMP-9 mRNA were quantified by quantitative real-time PCR （qRT-PCR）, the protein release and activation of MMPs were detected by gelatin zymography. HAb18G/CD147 antagonistic peptide AP-9 against CD147 was used to block CD147 function. Monocytes/macrophages derived from RA patients＇ synovial fluid were also investigated. Re- suits CypA increased MMP-9 expression significantly, not MMP-2, in the THP-1 cells. Cyclosporin A （CsA）, AP-9 dramatically decreased MMP-2 and MMP-9 expression respectively, both in the absence or presence of CypA. Similar effect of CypA on MMP-9 production was observed in monocytes/macrophages derived from RA patients＇ synovial fluid. Conclusion These findings suggest that CypA upregulates MMP-9 expression and adhesion of monocytes/macrophages by its direct binding to CD147, which may contribute to the destruction of cartilage and bone in RA.