旋毛虫感染不同时期对小鼠胶原诱导性关节炎影响的差异性观察?

观察旋毛虫感染的不同阶段对小鼠胶原诱导性关节炎（ Collagen?Ⅱ induced arthritis， CIA）的影响并初步探讨其机制。建立雄性DBA／1小鼠胶原（CⅡ）诱导性关节炎（CIA）模型，以旋毛虫肌幼虫（400条／只）分别于造模前14 d、造模当天感染小鼠。关节评分评价足爪关节病变的发生及严重程度。于胶原首次诱导后第50 d处死小鼠，取足爪关节切片观察组织病理学变化； ELISA检测血清抗CⅡ特异性IgG、IgG1、 IgG2a水平；分离脾淋巴细胞以ConA刺激培养， ELISA检测培养上清中IFN?γ、 IL?4、 IL?10、 IL?17和TNF?α细胞因子水平。结果显示，与单纯CIA造模组相比，预先14 d感染旋毛虫的CIA小鼠关节炎发病率、关节评分及组织学评分均显著降低，血清IgG1水平则显著升高，脾细胞培养上清Th2型细胞因子IL?4和调节性细胞因子IL?10水平显著增加。而造模当天感染旋毛虫的CIA小鼠关节评分和组织学评分显著升高，血清IgG2a水平显著升高，细胞培养上清Th1型细胞因子IFN?γ和促炎细胞因子IL?17、 TNF?α水平显著升高，且差异具有统计学意义。该结果表明，旋毛虫感染早期可加重胶原诱导性小鼠关节炎，而感染后期则对关节炎有一定抑制作用，提示旋毛虫对小鼠胶原诱导性关节炎的影响作用因感染时限的不同而存在差异，且该差异可能与不同感染时期诱导的Th反应类型的变化有关。

PHASE-SPECIFIC EFFECTS OF TRICHINELLA SPIRALIS INFECTION ON COLLAGEN-INDUCED ARTHRITIS IN MICE

The aim of this work is to examine the effect of different phases of Trichinella spiralis infection on collagen?induced arthritis ( CIA) in mice. Male DBA/1 mice were infected with T. spiralis 14 days prior to immunization of typeⅡcollagen ( CⅡ) or at the onset of immunization. Arthritic condition was scored for evaluation of the occurrence and severity of arthritis. The mice were sacrificed at day 50 after the first CⅡ immunization. Pathological change in the paws was evaluated by histological examination. Serum levels of anti?CⅡantibodies and cytokine production by concanavalin A ( ConA) ?stimulated spleen cells were measured by ELISA. The results showed that arthritic scores and histology scores were significantly decreased in CIA mice with prior 14?day T. spiralis infection compared with the CIA group. The levels of IgG1, IL?4 which were associated with the generation of T helper type 2 (Th2) cells and inhibitory cytokine (IL?10) were significantly increased in CIA mice with prior 14?day T. spiralis infection. However, the arthritis scores, histology scores and levels of Th1?derived IgG2a, IFN?γ and pro?inflammatory cytokines ( IL?17, TNF?α) were significantly increased in CIA mice with simultaneously T. spiralis infection. The results suggested that prior 14?day T. spiralis infection reduced the incidence and severity of CIA whereas simultaneously infection appears to aggravate CIA. The effect of T. spiralis infection on CIA may vary with the phases of infection, which might be associated with changing Th cells responses at different phases post infection.