【摘要】 目的:构建小鼠IL-18BP和IL-4融合表达的重组腺病毒载体(Ad mIL-18BP/mIL-4),对胶原诱导型关节炎(collagen-induced arthritis,CIA)小鼠进行局部关节基因治疗,观察小鼠血清IL-18表达水平。方法:采用雄性DBA-1/BOM小鼠,建立胶原诱导关节炎的小鼠模型。将融合表达小鼠IL-18BP和IL-4的重组腺病毒载体进行局部关节腔内注射后1、2、4周,采用酶链免疫吸附检测方法(ELISA),检测血清IL-18水平。同时设AdLacZ病毒对照组和PBS组织对照组。结果:CIA小鼠关节腔注射AdmIL-18BP/mIL-4后第1、2、4周,AdmIL-18BP/mIL-4治疗组的血清IL-18平均浓度分别为(36.5±5.4)ng/L、(32.5±3.2)ng/L、(28.7±2.9)ng/L,明显低于相应时间点AdLacZ对照组[(66.2±5.1)ng/L、(69.2±4.2)ng/L、(77.7±3.9)ng/L]和PBS对照组的水平[(67.3±7.1)ng/L、(71.9±1.8)ng/L、(78.7±4.1)ng/L],P均<0.01。但治疗组血清IL-18平均水平在不同时间点无显著性差别。结论:融合表达小鼠IL-18BP和IL-4的重组腺病毒基因治疗,能明显持续下调血清IL-18的表达水平,提示细胞因子基因治疗,可望为类风湿关节炎(RA)提供新的治疗策略。更多还原

【Abstract】 Objective:To investigate serum IL-18 levels in mice with collagen-induced arthritis treated by recombinant adenoviral vector containing mIL-18BP and mIL-4 fusion gene(AdmIL-18BP/mIL-4). Methods:Arthritis was induced by injection of collagen in male DBA-1/BOM mice.Mice with collagen-induced arthritis(CIA) were intra-articularly injected with 107pfu/6μL of AdmIL-18BP/mIL-4;and in mice of control groups AdLacZ or PBS were used.The animals were sacrificed at week 1,2 and 4 after treatment.Serum IL-18 levels were determined by ELISA at the different time points. Results:The mean serum levels of IL-18 at weeks 1,2,and 4 after injection of AdmIL-18BP/mIL-4 were(36.5±5.4)ng/L,(32.5±3.2)ng/L and(28.7±2.9)ng/L,respectively,which were significantly lower than those at the same time point of AdLacZ group [(66.2±5.1)ng/L,(69.2±4.2)ng/L and(77.7±3.9)ng/L ] and PBS group [(67.3±7.1)ng/L,(71.9±1.8)ng/L and(78.7±4.1)ng/L](P<0.01 at all time points).In the therapy group,there were no significant differences in the mean serum concentrations of IL-18 at all time points. Conclusion:The serum IL-18 levels in CIA mice are down-regulated by treatment of recombinant adenovirus containing mIL-18BP and mIL-4 fuse gene,which might be a promising therapeutic strategy for rheumatoid arthritis.更多还原