卵清蛋白雾化吸入诱导肠道菌群失调小鼠肺部过敏反应的发生

目的:在抗生素所致肠道菌群失调小鼠模型上采用卵清蛋白(OVA)雾化吸入激发,探讨气道变应性反应与肠道菌群失调的关系.方法:112只BALB/c小鼠分为6组:菌群失调Ⅰ组、对照Ⅰ组、菌群失调Ⅱ组、菌群失调加激发组、激发组、对照Ⅱ组.前2组和后4组分别于第6天和第14天时取盲肠内容物做细菌培养计数,后4组同时行支气管肺泡灌洗液(BALF)细胞分类计数、BALF和血清中OVA特异性IgE(OVA-sIgE)检测以及肺部病理观察;采用流式细胞术检测肺组织中Th1以及Th2细胞水平.结果:应用抗生素的小鼠出现肠道菌群失调,菌群失调加激发组小鼠肺部出现以嗜酸粒细胞和淋巴细胞为主的炎症细胞浸润,肺部黏液分泌明显增高,BALF中细胞总数、淋巴细胞、嗜酸粒细胞和中性粒细胞增加,OVA-sIgE水平显著增高,肺部Th2细胞水平增高,Th1细胞与对照组无差异.结论:抗生素致肠道菌群失调小鼠经过OVA雾化吸入后,可产生Th2细胞优势的变应性气道反应,提示抗生素所致肠道菌群失调是诱发哮喘等变应性疾病的危险因素之一.

Pulmonary allergic responses were drived by atomization with ovalbumin in BALB/c mice with intestinal microflora disruption

AIM:The mice in which the intestinal microflora disrulption resulted from antibiotic therapy are challenged by atomization with ovalbumin(OVA)to investigate the relation of allergic airway response and intestinal microflora disruption.METHODS:One hundred and twelve female BALB/c mice were devided at random into 6 groups.They were microbiota disruption Ⅰ group,control Ⅰ group,microbiota disruption Ⅱ group,microbiota disruption and challenge group,challenge groupand control Ⅱ group.Cecal contents were collected for quantitative analysis of the intastinal microflora in mice in the former two groups and in mice in the latter four groups on day 6 and day 14,respectively.On day 14,the bronchoalveolar lavage fluid(BALF)was collected for cells counting.OVA-specific IgE in BALF and sera was detected by ELISA.Parts of lungs were collected for histopathology and detection of Th1 and Th2 cell levels by flow cytometry.RFSULTS:The mice which were gived antibiotics suffered from intestinal microbiota disruption.In microbiota disruption and challenge group,eosinophil and lymphocyte infiltration was significant and mucus secretion was increased jn lung.The number of total cells,eosinophils,lymphocytes,neutrophils and OVA-specific IgE level were increased in BALF in microbiota disruption and challenge group.Th2 cell levels were increased and Th1 cell levels were not significantly different in microbiota disruption and challenge group compared with those in the control Ⅱgroup.CONCLUSION:The allergic(Th2)immune response can be induced by atomization with ovalbumin in the mice in which the intestinal microflora disruption is resulted from antibiotic therapy.The result suggests that the intestinal microflora disruption is a risk factor for allergy and asthma.