甲氨喋呤和雷公藤对类风湿关节炎滑膜细胞产生趋化因子的影响.docVIP

甲氨喋呤和雷公藤对类风湿关节炎滑膜细胞产生趋化因子的影响 作者：魏锦，袁国华，周京国，蔚芃，唐中，杨明辉，张国元 【摘要】 目的 探讨甲氨喋呤（MTX）和雷公藤多甙（TG）对类风湿关节炎（RA）滑膜细胞产生CC趋化因子受体5配体（CCL5）的影响。方法 分离于11例RA和6例骨关节炎（OA）的滑膜细胞行体外培养，并用细胞脂多糖（LPS）诱导CCL5产生，同时加入或不加入不同浓度的MTX或TG。采用酶联免疫吸附法（ELISA）测定培养上清液中的CCL5水平。结果 RA滑膜细胞体外自发产生CCL5水平高于OA滑膜细胞（Plt;0.05）；LPS刺激后，RA和OA滑膜细胞产生CCL5水平均较刺激前显著升高（P均lt;0.001），但二者间差异无显著性（Pgt;0.05）；MTX和TG均可显著抑制RA滑膜细胞产生CCL5，但二者抑制方式不同：MTX剂量在5～20ng/ml的剂量范围内呈现剂量依赖性效应，之后随剂量的增大，其抑制作用不再进一步增强。而TG 未显示出剂量依赖性抑制效应，仅在剂量达到或超过60ng/ml时出现比MTX更显著的抑制作用。进一步分析发现，TG抑制CCL5产生与其所致的滑膜细胞死亡相关。结论 RA滑膜细胞产生CCL5增高，MTX和TG均可显著抑制CCL5的产生，其中TG抑制CCL5产生与其细胞毒作用有关。 【关键词】 关节炎 类风湿 趋化因子受体5配体 滑膜细胞 The inhibitory effects of methotrexate and tripterygium glycosides on chemokine CCL5 production in synoviocytes from patients with rheumatoid arthritis 【Abstract】 Objective To determine the inhibitory effects of methotrexate (MTX) and tripterygium glycosides (TG) on chemokine CCL5 production in synoviocytes isolated from patients with rheumatoid arthritis (RA).Methods Synoviocytes， isolated from RA patients and patients with osteoarthritis (OA)， were cultured and stimulated with or without lipopolysaccharide (LPS) in the presence or absence of different dosage of MTX or TG. CCL5 level in cultural supernatants was measured by enzyme-linked immunosorbent assay (ELISA).Results RA synoviocytes spontaneously produced higher level of CCL5 than OA synoviocytes did. Both MTX and TG were found to significantly inhibit LPS-induced CCL5 production in RA synoviocytes. Moreover， the inhibitory effect of MTX appeared to be in a dosage dependent manner in the concentration ranged from 0- 20ng/ml. Whereas TG showed its inhibitory effect only when it reached at the concentration of 60ng/ml. Furthermore， the inhibitory effect of TG was found to be correlated with TG-induced cell death.Conclusion The increased production of CCL5 by RA synoviocytes indicates a role of CCL5 in the pathogenesis of RA， and the disease modifying effects of MTX and TG migh