目的：探讨白细胞介素18（interleukin 18，IL -18）对分泌性中耳炎（otitis media with effusion ，OME）模型大鼠中耳炎症细胞的增殖情况以及干扰素γ（interferon γ，IFN -γ）和白细胞介素4（interleukin 4，IL -4）表达的影响。方法18只SD大鼠随机分为对照组（A组）、OM E模型组（B组）和IL -18注射组（C组），每组各6只（12耳），B组和C组采用卵清蛋白（ovalbumin ，OVA）腹腔注射致敏后耳内激发制成OME模型，C组于OVA全身致敏及耳内激发的同时，在实验第1、2、7、8、15、16 d进行腹腔注射IL -181μg加生理盐水0．2 ml ，A组和B组在相同时间点腹腔注射生理盐水0．2 ml。HE染色观察各组中耳黏膜病理变化及炎症细胞的改变，ELISA法测定各组大鼠中耳腔灌洗液中T辅助细胞（T helper cell ，Th）分泌Th2型细胞因子-IL -4和Th1型细胞因子-IFN -γ的含量。结果 C组大鼠中耳黏膜组织炎症反应较B组无明显减轻，中耳黏膜下层和骨髓腔中中性粒细胞数量较B组显著增多（P＜0．05），嗜酸粒细胞数量与B组比较稍减少（P＞0．05），但仍明显多于A组（P＜0．05）；C 组中耳灌洗液Th1型细胞因子IFN -γ含量明显高于B组与A组（P＜0．05），Th2型细胞因子IL -4含量较B组稍有增高（P＞0．05）；但B组和C组IL -4含量均明显高于A组（P＜0．05）；A、C组Th1/Th2比值虽高于B组，但差异无统计学意义（P＞0．05）。结论 IL -18诱导OME模型大鼠中耳微环境中IFN -γ合成显著增高，虽然一定程度上缓解了OME大鼠中耳Th1/Th2失衡状态，但是仍存在以Th细胞过度活化、Th1和Th2型细胞因子过度分泌的免疫反应紊乱状态。%Objective To investigated the effects of IL -18 on middle ear allergic inflammation in rat model of OME .Methods Eighteen SD rats were randomly divided into three group :group A(control group ,n=12 ears) , group B (OME model group ,n=12 ears) ,group C (IL -18 injectiion group ,n=12 ears) .The rat model of OME was established by sensitizing with ovalbumin (OVA) and later challenging in tympanic bullae .Recombinant rat IL-18 (1 μg ,+0 .2 ml saline ,) were injected in group C at 1 ,2 ,7 ,8 ,15 ,16 day .At the same time sacle ,0 .2 ml sa-line ,instead of IL -18 ,were intraperitoneal injection in group A and B .The morphologic changes of the middle ear epithelial cells and inflammatory cells infiltration were observed under light microscope .The level of IFN -γand IL-4 in tympanic lavage fluid(TLF) were determined by ELISA .Results Pathological examination showed that middle ear mucosa inflammation and eosinophil infiltration in group C were no less severe than group B .The numbers of neutrophils in group C increased significantly compraring with group B (P<0 .05) .Numbers of eosinophils in group C were slightly increased comparing with group B (P>0 .05) ,while significantly greater than that in group A (P<0 .05) .ELISA showed that the level of IFN -γ in group C was stronger than that in group B and A (both P<0 .05) .As compared to the group A ,the expression of IL -4 in group B and group C were remarkably stronger (both P<0 .05) ,no significant difference was found between group B and group C (P>0 .05) .Addtionally ,there was no significant difference in the ratio of Th1 /Th2(IFN -γ/IL -4)between group B and group C (P>0 .05) . Conclusion IL -18 acts as an immune regulatory factors ,significantly increases Th1 cytokine IFN -γ.Although to some extent alleviate the OME rat middle ear Th1 /Th2 imbalance ,there is still excessive activation of Th cells . Th1 and Th2 cells factor are excessive for the secretion disorder of the immune response status .The OME rat mid-dle ear allergic inflammation has not been fundamentally alleviated ,the underlying mechamism should be further studied .
展开▼
