屋尘螨2种致敏方式诱导的小鼠气道炎症表型的比较分析

目的比较屋尘螨(house dust mite, HDM)2种不同致敏方式对小鼠气道炎症表型的不同影响。方法24只BALB/c小鼠随机分为3组,每组8只,PBS组和鼻滴法组小鼠于实验第1天、第7天、第14天、第21天经鼻腔分别滴注50μl PBS液或HDM液(100μg)。经腹腔注射组小鼠于实验第1、14、21天经腹腔注射50μl HDM液(40μg),于实验第26天、第27天、第28天雾化吸入HDM液(40μg)20min。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(bronchoalveolar lavage fluid, BAL)进行细胞计数和分类；ELISA法检测BAL中CXCL1、CXCL2、CCL11、IL-5、IFN-γ、IL-10和IL-17的表达及血清免疫球蛋白(HDM-IgG1、HDM-IgG2a、HDM-IgE)的含量；对肺组织PAS染色后进行病理学观察。结果 鼻滴法诱导了以中性粒细胞为主的气道炎症并伴CXCL1蛋白水平升高、血清HDM-IgG1含量增加及肺组织高脚杯细胞增多等病理学改变,但血清HDM-IgE的含量和气道反应性未见改变。经腹腔注射法则诱导了更加剧烈的气道炎症反应(以嗜酸性粒细胞为主)、BAL中CXCL1、IL-5蛋白水平升高、血清免疫球蛋白(HDM-IgG1、HDM-IgG2a、HDM-IgE)含量增加、气道反应性下降以及肺组织病理学改变。结论 HDM鼻滴法和经腹腔注射法诱导了不同类型的小鼠气道炎症反应。
Objective To compare the phenotypes of airway inflammation by using house dust mite(HDM) with two different methods in mice. Methods Twenty four female BALB/c mice were divided into 3 groups with 8 in each group. In PBS and intranasal group, the mice received an intranasal instillation of PBS or HDM(100μg) on 1st, 7th, 14th and 21st day, respectively. In intraperitoneal group, the mice received an intraperitoneal injection of HDM(40μg) on 1st, 14th and 21st day, and then nebulization of HDM (40μg) for 20 min on 26th, 27th and 28th day. After the final challenge, airway responsiveness(AR), immunological status and histological changes in the airways were examined. ResultsIntranasal instillation elicited a neutrophil-dominated airway inflammation which was accompanied by an elevated protein level of CXCL1 in bronchial alveolar lavage(BAL), an increased production of serum HDM-IgG1 and subsequent histological changes including goblet cell hyperplasia(GCH), but the serum HDM-IgE was not changed. Intraperitoneal injection led to a more robust airway inflammation(mainly eosinophils), increase of CXCL1 and IL-5 in the BAL, rise in serum immunoglobins levels(HDM-IgG1, HDM-IgG2a, HDM-IgE) and goblet cell hyperplasia in the lung tissue. Conclusion The two sensitizing methods of HDM induced different types of airway inflammation in mice