地塞米松抑制烟曲霉菌暴露的支气管哮喘大鼠肺组织IL-33的表达

摘要

目的 研究烟曲霉菌暴露对支气管哮喘大鼠肺组织IL-33水平的影响及地塞米松的作用.方法 将24只Wistar大鼠随机分为A组(正常对照组)、B组(哮喘组)、C组(烟曲霉菌暴露组)、D组(地塞米松干预组),每组6只.B、C、D组均以卵白蛋白(ovalbumin,OVA)致敏、激发的方法构建哮喘模型;C、D组在哮喘模型构建成功后,给予烟曲霉菌孢子鼻腔滴入;D组在OVA激发阶段给予地塞米松干预;A组则予等量生理盐水致敏、激发、滴鼻作为对照.通过气道高反应性检测、嗜酸性粒细胞百分比及血清IgE水平确定哮喘模型的建立,ELISA法及qRT-PCR法检测肺组织IL-33的表达,大鼠肺组织和全血于马铃薯葡萄糖琼脂培养基(potato dextroseagar,PDA)上培养24 h后观察烟曲霉菌菌落生长情况.结果 B、C组与A组比较,肺泡灌洗液中嗜酸性粒细胞百分比、血清IgE水平及肺组织IL-33的表达均明显升高(P＜0.05),且C组比B组升高更明显.各组间气道反应性指标sRaw变化值差异不明显.D组与C组比较,嗜酸性粒细胞百分比及肺组织IL-33的表达均明显降低(P＜0.05),血清IgE水平降低不显著,但肺组织烟曲霉菌培养阳性率高于C组.结论 糖皮质激素(地塞米松)能够抑制烟曲霉菌暴露的支气管哮喘大鼠肺组织IL 33的表达,但增加了气道真菌定植的风险,针对IL-33的阻断治疗有待进一步研究.%Objective To investigate the levels of IL-33 in the lung induced by Aspergillus fumigatus (A.fumigatus) exposure in bronchial asthmatic rats and the effects of dexamethasone.Methods Twenty-four Wistar rats were randomly and equally divided into group A (normal control),group B (asthma group),group C (A.fumigatus-exposed group),and group D (dexamethasone-treated group).B,C and D group were sensitized and challenged with ovalbumin (OVA) to establish asthmatic models.Then,group C and D were given A.fumigatus spores intranasally.Group D was pre-treated with dexamethasone during ovalbumin challenge.Group A was sensitized and challenged intranasally with normal saline as control.Airway hyperresponsiveness,eosinophils percentage and serum IgE levels were measured to confirm the establishment of asthmatic model.Expression of IL-33 in the lung were quantified by ELISA and qRT-PCR.Lung tissues and blood were plated on the potato dextrose agar (PDA) medium and cultivated for 24 h to measure the number of colony.Results Eosinophils percentage in bronchoalveolar lavage fluid (BALF),IgE levels in serum and IL-33 levels in the lung in group B and C were much more higher than in group A (P＜0.05),and the increasing range in group C was more obvious than group B.However,the changes of sRaw values in these groups had no statistical significance.Esosinophils percentage in BALF and IL-33 levels in the lung were significantly decreased (P＜0.05),and IgE levels in serum was slightly decreased (P＞0.05) in group D when compared with group C,but the ratio of A.fumigatus colonization in the lung was higher than group C.Conclusions Dexamethasone can inhibit the expression of IL-33 in the lung induced by A.fumigatus exposure in an asthmatic rat,but it also increases the risk of fungal colonization in the airway.Anti-IL-33 antibody treatment needs further research.