日本血吸虫感染小鼠下调IL-17抑制尘螨过敏性哮喘及其机制的实验研究

A study on how dust mite allergic asthma is inhibited by a Schistosoma japonicum infection via down-regulation of IL-17 and that mechanism

目的探讨日本血吸虫感染对屋尘螨(HDM)诱导的过敏性哮喘的抑制及其机制。方法建立小鼠C57BL/6J的日本血吸虫感染模型,5周后用HDM按30μl/只剂量诱导哮喘,同时设立野生型小鼠作为健康对照组。待诱导哮喘后17 d解剖小鼠,收集肺泡灌洗液,用Kwik-Diff染色后作炎症细胞分类并计数,采用ELISA法检测肺泡灌洗液中IL-17水平。取一侧肺组织行石蜡切片,PAS染色,在显微镜下观察肺组织病理变化;Trizol试剂提取另一侧肺组织总RNA,应用荧光定量PCR检测Eotaxin、Gob-5等炎症基因的mRNA表达水平。结果与单纯HDM诱导组相比,血吸虫感染可显著降低HDM诱导的肺组织中的炎症反应。肺泡灌洗液中炎症细胞数量及IL-17水平显著低于单纯HDM诱导组(P均<0.05)。荧光定量PCR检测血吸虫感染小鼠肺组织中HDM诱导炎症相关因子Eotaxin、Gob-5的mRNA表达水平显著降低。结论日本血吸虫感染可通过下调IL-17细胞因子水平抑制HDM诱导的过敏性哮喘。

Objective To investigate how allergic asthma induced by house dust mites(HDMs)is inhibited by a Schistosoma japonicum infection and that mechanism.Methods A mouse model of S.japonicum infection was created with C57 BL/6 J.After 5 weeks,asthma was induced by HDMs at 30μl/mouse.Wild-type mice served as normal controls.Seventeen days later,bronchoalveolar lavage(BAL)fluids were collocated for cell counting and Kwik-Diff staining.The BAL fluids were centrifuged to determine the level of IL-17 using ELISA.For lung histology,paraffin sections of lung tissues were processed for periodic acid-Schiff(PAS)staining to observe pathological changes.Levels of mRNA of cytokines such as eotaxin and Gob-5 were determined using real-time quantitative PCR.Results Lung histology indicated that there were more inflammatory cells infiltrating around bronchi and blood vessels in the HDM group and the SJ+HDM group.An S.japonicum infection effectively inhibited the pulmonary inflammatory response.Some trachea mucosa epithelium was necrotic and had sloughed off,and hypertrophic and hyperplastic goblet cells around bronchi secreted a lot of mucus,but the amount of secretion in the SJ+HDM group was less than that in the HDM group.The total number of BAL cells and neutrophils decreased significantly in the SJ+HDM group compared to numbers in the HDM group.In the SJ+HDM group,the levels of IL-17 in BAL were lower than those in the HDM group.Real-time quantitative PCR yielded similar results:levels of eotaxin and Gob-5 mRNA in the S.japonicum infection group were lower than those in the HDM group.Conclusion An S.japonicum infection inhibits dust mite allergic asthma by down-regulating IL-17.