论文部分内容阅读
目的探讨多房棘球幼(E.m)感染所致的免疫应答偏倚对实验性类风湿性关节炎(CIA)的免疫调节作用。方法分别建立雌性C57小鼠胶原性关节炎模型(CIA组)、多房棘球蚴感染模型(E.m组)和多房棘球蚴感染后类风湿性关节炎诱导模型(E.m+CIA组),利用实时荧光定量RT-PCR和酶联免疫吸附试验(ELISA)检测小鼠足爪组织、外周血及脾脏细胞中Th17细胞相关因子及转录因子水平,实验设阴性对照组(Control组)。组间比较采用非参数秩和检验两个独立样本比较法(M-W法);采用Spearman线性相关性分析方法分析细胞因子及转录因子之间的相关关系。结果外周血及脾脏细胞中IL-17A、IL-1β、IFN-γ水平在E.m+CIA组18.93(14.90~20.53)pg/ml、18.93(14.90~20.53)pg/ml,4.18(1.79~4.45)pg/ml、4.182(1.794~4.446)pg/ml,14.79(0.64~29.38)pg/ml、14.79(0.64~29.38)pg/ml,显著低于CIA组16.47(15.41-19.46)pg/ml、16.47(15.41~19.46)pg/ml,161.60(125.40~222.20)pg/ml、367.2(240.4~550.3)pg/ml,29.89(19.93~58.95)pg/ml、29.89(19.93~58.95)pg/ml(P<0.05或P<0.01);E.m+CIA组IL-4、IL-6等抗炎相关因子水平11.68(11.00~12.85)pg/ml、11.68(11.00~12.85)pg/ml,450.40(292.80~697.50)pg/ml、450.40(292.80~645.60)pg/ml,较其他组显著升高(P<0.05或P<0.01)。小鼠足爪中IL-17A及RORrt mRNA相对表达量在E.m+CIA组13.29(5.38~18.93),1.07(0.78~6.99)较其他组降低。结论 E.m感染诱导的Th2优势应答可使CIA不能有效启动致病性Th1免疫应答,抑制CIA小鼠过度的Th17应答,从而减轻RA炎症损伤。
Objective To investigate the immunomodulatory effect of immune response bias induced by E.m infection on experimental rheumatoid arthritis (CIA). Methods C57 mice model of collagen arthritis (CIA group), Echinococcus multilocularis infection group (Em group), and Echinococcus multilocularis infection induced rheumatoid arthritis model (E.m CIA group ). The levels of Th17 cell related factors and transcription factors in foot paw tissue, peripheral blood and spleen of mice were detected by real-time fluorescence quantitative RT-PCR and enzyme-linked immunosorbent assay (ELISA). Two independent sample comparison methods (M-W method) were used to compare between two groups by nonparametric rank sum test. Spearman’s linear correlation analysis method was used to analyze the correlation between cytokines and transcription factors. Results The levels of IL-17A, IL-1β and IFN-γ in peripheral blood and spleen cells were significantly increased in the group of E.m + CIA at 18.93 (14.90-20.53) pg / ml and 18.93 (14.90-20.53) pg / ml, 4.45) pg / ml, 4.182 (1.794-4.446) pg / ml, 14.79 (0.64-29.38) pg / ml and 14.79 (0.64-29.38) pg / ml were significantly lower than that of CIA group , 16.47 (15.41-19.46) pg / ml, 161.60 (125.40- 222.20) pg / ml, 367.2 (240.4-550.3) pg / ml, 29.89 (19.93- 58.95) pg / ml, 29.89 (P <0.05 or P <0.01). The levels of IL-4, IL-6 and other anti-inflammatory cytokines were 11.68 (11.00-12.85) pg / ml, 11.68 (11.00-12.85) pg / ml and 450.40 (292.80 ~ 697.50) pg / ml and 450.40 (292.80 ~ 645.60) pg / ml respectively, which were significantly higher than the other groups (P <0.05 or P <0.01). The relative expression levels of IL-17A and RORrt mRNA in foot paw of mice in group E.m + CIA decreased from 13.29 (5.38 ~ 18.93), 1.07 (0.78 ~ 6.99) in E.m + CIA group. Conclusions The predominant Th2 response induced by E.m infection can prevent CIA from effectively activating the pathogenic Th1 immune response and inhibiting the excessive Th17 response in CIA mice, thus reducing the inflammatory injury of RA.