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甲氨蝶呤对类风湿关节炎滑膜细胞增殖及细胞周期的影响 被引量:2

Effects of Methotrexate on Cell Proliferating Efficiency and Cell Cycling of Synovial Fibroblasts in Patients with Rheumatoid Arthritis
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摘要 目的 研究甲氨蝶呤 (MTX)对类风湿关节炎 (RA)滑膜细胞增殖及细胞周期的影响 ,揭示MTX治疗RA的机制。方法 应用克隆形成实验和流式细胞术分别测定RA患者滑膜细胞的增殖水平和细胞周期。结果 加入不同浓度MTX (0 2~ 2 μmol/L)的实验组 ,RA患者滑膜细胞克隆形成率均显著低于未加MTX的空白对照组 (P<0 0 5 ) ;细胞周期分析显示加入不同浓度MTX后第 5、 8天 ,细胞停留在G1期的比例比空白对照组明显增加 (P <0 0 5 ) ,而S、G2 期的细胞比例则明显减少 (P <0 0 5 ) ;MTX能明显抑制滑膜细胞的增殖水平 ,并呈剂量依赖性。结论 MTX治疗RA ,主要作用于RA患者滑膜细胞的增殖及增殖相关的病理过程。 Objective To investigate the effects of methotrexate (MTX) on cell proliferation and cell cycling of synovial fibroblasts in patients with rheumatoid arthritis (RA), and evaluate the mechanism of MTX in treating RA. Methods The levels of cell proliferation and cell cycle of synovial fibroblasts treated or untreated with MTX in patients with rheumatoid arthritis were measured by cloning efficiency assay and fluorescence-activated cell sorting (FACS) method respectively. Results The cloning efficiencies of MTX-treated (0.2 _mol/L to 2 _mol/L) synovial fibroblasts in patients with RA were significantly decreased as compared with corresponding untreated group (P<0.05). FACS assay showed the rate of MTX-treated synovial fibroblasts in patients with RA in G_1 phase was significantly increased as compared with untreated group (P<0.05) on the day 5,8, but the rate of synovial fibroblasts in S phase and G_2 phase was significantly decreased as compared with untreated group (P<0.05). MTX inhibited proliferation of synovial fibroblasts in a dose-dependent manner. Conclusion MTX can be used to treat RA by inhibiting proliferation and proliferation-dependent processes of synovial fibroblasts in patients with RA.
出处 《华中科技大学学报(医学版)》 CAS CSCD 北大核心 2004年第5期599-601,共3页 Acta Medicinae Universitatis Scientiae et Technologiae Huazhong
基金 湖北省科技攻关计划资助项目 (No .2 0 0 2AA30 1C4 7)
关键词 滑膜细胞 MTX RA 增殖 细胞周期 治疗 甲氨蝶呤 克隆 病理过程 水平 arthritis, rheumatoid synovial fibroblasts methotrexate cell cycle
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  • 1Quemeneur L, Gerland L M, Flacher M et al. Differential control of cell cycle, proliferation, and survival of primary T lymphocytes by purine and pyrimidine nucleotides. J Immunol, 2003, 170:4986
  • 2Sgambato A, Camerini A, Pani G et al. Increased expression of cyclin E is associated with an increased resistance to doxorubicin in rat fibroblasts. Br J Cancer,2003, 88:1956
  • 3Fairbanks L D, Ckemann K R, Qiu Y et al. Methotrexate inhibits the first committed step of purine biosynthesis in mitogen-stimulated human T-lymphocytes: a metabolic basis for efficacy in rheumatoid arthritis? Biochem J, 1999, 342:143
  • 4Perlman H, Bradley K, Liu H et al. IL-6 and matrix metalloproteinase-1 are regulated by the cyclin-dependent kinase inhibitor p21 in synovial fibroblasts. J Immunol, 2003, 170: 838

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