慢性烟曲霉菌暴露对哮喘加重的免疫机制研究

发布时间：2018-02-02 20:48

本文关键词： 烟曲霉哮喘 IgE 气道高反应性嗜酸性粒细胞糖皮质激素受体　出处：《上海交通大学》2015年硕士论文　论文类型：学位论文

【摘要】：第一章烟曲霉孢子吸入对哮喘大鼠气道炎症、气道反应性以及血清总IgE水平的影响目的:探讨烟曲霉孢子雾化吸入对哮喘模型大鼠气道内嗜酸性炎症、气道高反应性(airway hyperresponsiveness,AHR)及血清中总IgE水平的影响。方法:将18只Wistar雄性大鼠随机分为正常组、哮喘组和烟曲霉雾化吸入组。以卵白蛋白注射致敏、雾化激发的方法构建大鼠哮喘模型。烟曲霉暴露组在哮喘模型构建成功后,反复给予烟曲霉雾化吸入。测定每组大鼠对Mch(methacholine,乙酰甲胆碱)的气道反应性,之后采集肺组织与血液标本,测定气道内炎症以及血清总IgE水平的变化情况。结果:烟曲霉孢子暴露进一步加重了哮喘大鼠气道炎症及气道高反应性(Mch在12.5、25及50 mg/ml浓度下P值均小于0.05),血清总IgE水平也有显著的提升(P0.05)。各组大鼠血IgE水平与气道反应性指标PC100(将Penh值升高到基础水平2倍时的Mch浓度定为PC100)密切相关(r=-0.873,P0.01);同时与BALF内炎性细胞中嗜酸粒细胞的百分比也呈现明显的相关性(r=0.937,P0.01)。结论:反复的烟曲霉菌孢子雾化吸入能够促进哮喘模型大鼠肺组织内嗜酸粒细胞浸润及气道高反应性的恶化,而嗜酸粒细胞炎症及气道高反应性的加重可能与血清总IgE水平的升高密切相关。第二章糖皮质激素受体水平变化在烟曲霉菌孢子加重哮喘中的作用目的:烟曲霉菌是否能够影响哮喘大鼠肺组织内GR(糖皮质激素受体)水平,从而导致哮喘加重、激素耐受,目前尚不清楚。本研究的主要目的就是要探究烟曲霉菌对大鼠肺组织内GR表达情况的影响。方法:构建经典的OVA诱导的大鼠哮喘模型,之后进行慢性烟曲霉菌孢子的雾化吸入。观察曲霉菌孢子雾化吸入后哮喘大鼠气道炎症以及气道高反应性的变化情况;通过实时荧光定量PCR以及蛋白免疫印记的方法测得GR受体水平变化。结果:反复烟曲霉菌孢子吸入能够显著促进OVA哮喘大鼠肺组织气道炎症以及气道高反应性的加重(P0.05);并且,在哮喘模型的基础上吸入烟曲霉菌孢子,肺组织内GR受体出现了明显下调(P0.05)。结论:烟曲霉菌孢子吸入能够诱导哮喘大鼠肺组织内GR受体水平的下调,这可能是引起哮喘症状加重以及激素抵抗的重要原因。
[Abstract]:Chapter 1 effects of Aspergillus fumigatus Spore inhalation on Airway inflammation, Airway responsiveness and Serum Total IgE level in Aspergillus fumigatus Rats objective: to investigate the effect of Aspergillus fumigatus aerosol inhalation on airway eosinophilic inflammation in asthmatic rats. Airway hyperresponsiveness and airway hyperresponsiveness. Methods: eighteen Wistar male rats were randomly divided into normal group, asthma group and Aspergillus fumigatus aerosol inhalation group, and were sensitized with ovalbumin. Aspergillus fumigatus exposure group was given Aspergillus fumigatus aerosol inhalation repeatedly after the model was successfully constructed. The Mch(methacholine of each group was measured. The airway reactivity of methacholine was then collected from lung tissues and blood samples. Results: exposure to Aspergillus fumigatus spores further aggravated airway inflammation and airway hyperresponsiveness in asthmatic rats. P values were less than 0.05 at 25 and 50 mg/ml concentrations. The serum total IgE level was also significantly increased (P 0.05). The level of serum IgE and the airway responsiveness index PC100 in each group were also significantly increased (P < 0.05). The concentration of Mch was determined as PC100 when the Penh value was doubled to the basic level). P0.01; At the same time, the percentage of eosinophils in inflammatory cells in BALF was also significantly correlated with rrm0.937. Conclusion: repeated inhalation of Aspergillus fumigatus spores can promote the infiltration of eosinophils and the deterioration of airway hyperresponsiveness in asthmatic rats. The increase of eosinophils inflammation and airway hyperresponsiveness may be closely related to the increase of serum total IgE level. Chapter 2 the role of glucocorticoid receptor level in Aspergillus fumigatus spores exacerbating asthma:. Whether Aspergillus fumigatus can affect the expression of GR1 in lung tissue of asthmatic rats. Glucocorticoid receptor. This leads to asthma exacerbation, hormone tolerance. The main purpose of this study is to explore the effect of Aspergillus fumigatus on the expression of gr in rat lung tissue. Methods: the classical rat asthma model induced by OVA was constructed. The changes of airway inflammation and airway hyperresponsiveness of Aspergillus fumigatus were observed after inhalation of Aspergillus fumigatus spores. The level of gr receptor was measured by real-time fluorescence quantitative PCR and protein imprinting. Results:. Repeated aspergillus fumigatus spores inhalation significantly promoted airway inflammation and airway hyperresponsiveness in OVA asthmatic rats. P0.05; In addition, Aspergillus fumigatus spores were inhaled on the basis of asthma models. Conclusion: Aspergillus fumigatus spores inhalation can induce the down-regulation of gr receptor level in lung tissue of asthmatic rats. This may be an important cause of exacerbation of asthma symptoms and hormone resistance.
【学位授予单位】：上海交通大学
【学位级别】：硕士
【学位授予年份】：2015
【分类号】：R562.25

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