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多房棘球蚴感染对胶原蛋白诱导小鼠自身免疫性关节炎的影响研究

The effects of infection with Echinococcus multilocularis on autoimmune arthritis induced by collagen in C57 mice
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摘要 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 explore the effects of immune response bias caused by infection with Echinococcus multilocularis on immune system regulation as a result of experimentally induced rheumatoid arthritis. Methods Thirty-two 5-6week old C57 mice were randomly divided into four groups(n=8in each group):(1)negative control group(control),(2)E.multilocularis group:healthy mice were inoculated with E.multilocularis,(3)CIA group:rheumatoid arthritis was induced in healthy mice using collagen,(4)E.multilocularis+CIA group:healthy mice were infected with E.multilocularis and then rheumatoid arthritis was induced with collagen.The levels of Th17 cells and Th17-related cytokines in the spleen and peripheral blood and the tissue of the paw were detected using RT-PCR and ELISA.Groups were compared using a non-parametric rank sum test for two independent samples.Spearman linear correlation analysis was used to study the relationship between cytokines and transcription factors. Results In the E.multilocularis+CIA group,the level of IL-17 Ain peripheral blood was 18.93pg/ml(range:14.90-20.53pg/ml)and that in spleen cells was 18.93pg/ml(range:14.90-20.53pg/ml),the level of IL-1βin peripheral blood was 4.18pg/ml(range:1.79-4.45pg/ml)and that in spleen cells was 4.182pg/ml(range:1.794-4.446pg/ml),and the level of IFN-γin peripheral blood was14.79pg/ml(range:0.64-29.38pg/ml)and that in spleen cells was 14.79pg/ml(range:0.64-29.38pg/ml).In the CIA group,the level of IL-17 Ain peripheral blood was 16.47pg/ml(range:15.41-19.46pg/ml)and that in spleen cells was 16.47pg/ml(range:15.41-19.46pg/ml),the level of IL-1βin peripheral blood was 161.60pg/ml(range:125.40-222.20pg/ml)and that in spleen cells was 367.2pg/ml(range:240.4-550.3pg/ml),and the level of IFN-γin peripheral blood was 29.89pg/ml(range:19.93-58.95pg/ml)and that in spleen cells was 29.89pg/ml(range:19.93-58.95pg/ml).The levels of IL-17 A,IL-1β,and IFN-γin peripheral blo
出处 《中国病原生物学杂志》 CSCD 北大核心 2016年第10期917-923,共7页 Journal of Pathogen Biology
基金 新疆维吾尔自治区自然科学基金项目(No.2014211C081)
关键词 多房棘球蚴病 类风湿性关节炎 辅助性T细胞 免疫应答 Echinococcus multilocularis rheumatoid arthritis T helper cell immune response
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