CpG-ODN气道内应用抑制哮喘小鼠过敏性气道炎症及GATA-3的表达

Intratracheal CpG-ODN administration inhibit allergic airway inflammation and GATA-3 expression of asthmatic mice

目的 研究气道内应用CpG寡脱氧核苷酸 (CpG ODN)对小鼠哮喘模型气道过敏性炎症的治疗作用及对肺内GATA 3表达的影响。方法 鸡卵蛋白 (OVA)免疫BALB c小鼠建立哮喘模型 ,激发后 1h气道内滴入 10 0 μgCpG ODN ,处死动物后观察支气管肺泡灌洗液 (BALF)中白细胞总数、嗜酸性粒细胞百分比 (EOS % )的变化及IL 4、IL 5、IL 12、IFN γ的含量变化。取肺组织行病理切片HE染色、AB PAS染色检查 ,观察小鼠气道炎症情况 ,免疫组化染色观察CpG ODN对小鼠哮喘模型肺部GATA 3表达的影响。结果 CpG ODN治疗组BALF中IL 12和IFN γ的产生增加 ,IL 4、IL 5的产生减少 ,BALF中细胞总数及嗜酸性粒细胞比例降低 ,肺部炎症情况明显减轻 ,肺血管周围及支气管周围表达GATA 3的细胞数较哮喘模型组及对照寡核苷酸治疗组明显减少。结论 哮喘小鼠激发阶段气道内滴入CpG可能通过诱导IL 12、IFN γ产生 ,抑制GATA 3的表达 ,导致TH2型细胞因子的产生减少 ,从而减轻哮喘气道过敏性炎症。

Objective To evaluate the therapeutic effect on allergic airway inflammation and influence on pulmonary GATA-3 expression of asthmatic mouse model by the intratracheally administered CpG oligodeoxynucleotide (CpG-ODN). Methods The model was constructed by OVA immunization of BALB/c mice. 100μg CpG-ODN was dripped into trachea one hour after stimulation and WBC count,eosinophil %(EOS%),IL-4,IL-5,IL-12,IFN-γ level in BALF were checked. GATA-3 expression was observed by pulmonary immnohistochemical staining. Results In CpG-ODN treated group,IL-12,IFN-γ in bronchoalveolar lavage fluid(BALF) increased but IL-4,IL-5, WBC count and EOS% decreased. The pulmonary inflammation was remarkably relieved and cell number expressing GATA-3 around the pulmonary vessels and bronchi was decreased as comparing with control group. Conclusion CpG-ODN can induce IL-12,IFN-γ production and inhibit GATA-3 expression when give intratracheally during stimulation phase,that resulted in T H2 cytokines decrease and relief of asthmatic airway inflammation.