屋尘螨在诱导BALB／c小鼠混合型气道炎症中的作用及致病机制探讨

House dust mite induces mixed allergic airway inflammation in a murine asthma model

目的探讨屋尘螨（HDM）抗原在小鼠模型中诱导混合型气道炎症中的作用及其机理，为支气管哮喘的临床诊断和治疗提供理论依据。方法BALB／c小鼠于实验第0天、7天、14天、21天、28天和35天进行PBS或HDM提取液（50μg或100μg）滴鼻。采用头体积描记法测量小鼠的气道反应性；对支气管肺泡灌洗液（BAL）进行细胞计数和分类；酶联免疫法（ELISA）检测BAL中CXCL1、CXCL2、CCL11（eotaxin）、IL-5、IFN1、IL-10和IL-17的含量及血清总IgE，HDM特异性IgG1、IgG2a；采用实时荧光定量PCR检测肺组织中相关基因mRNA表达；并对肺组织PAS染色后进行病理学观察。结果HDM抗原引起了以中性粒细胞和嗜酸性粒细胞为主的混合型气道炎症、血清HDM特异性IgG1的升高及高脚杯细胞增生（GCH）等组织学变化，其混合型气道炎症可能与CXCL-1和IL-5等细胞因子的分泌增多有关，是固有免疫和适应性免疫共同活化的结果。这种炎症表型在经高浓度HDM（100μg）致敏的小鼠中表现得更为显著。结论HDM过敏原在小鼠模型中诱导了中性粒细胞和嗜酸性粒细胞的共同活化。

Objective To explore the potential role of house dust mite （HDM） allergen in the patho- genesis of mixed airway inflammation and provide evidence for the diagnosis and treatment of asthma. Methods BALB/c mice received an intranasal instillation of PBS or HDM extract （50 μg or 100μg） on days O, 7, 14, 21, 28, 35. After the final challenge, airway responsiveness （AR）, histological changes in the airways and immunological status were examined. Results HDM allergen elicited a mixed airway inflammation of neu- trophils and eosinophils which were accompanied by an increased production of serum HDM-IgG1 and subsequent histological changes including goblet cell hyperplasia （GCH）. The mixed airway inflammation was asso- ciated with the upregulation of ehemokines and cytokines including CXCL1 and IL-5, representing the activation of innate immune response and adaptire immune response. This phenotype was more pronounced in mice sensi- tized by the highest tested HDM extract concentration （100 μg）. Conclusion Neutrophils as well as eosino- phils were activated by the sensitization of HDM allergen in the experimental mouse model.