發(fā)布時間：2018-02-02 20:48

  本文關(guān)鍵詞： 煙曲霉 哮喘 IgE 氣道高反應(yīng)性 嗜酸性粒細胞 糖皮質(zhì)激素受體　出處：《上海交通大學》2015年碩士論文　論文類型：學位論文

【摘要】：第一章煙曲霉孢子吸入對哮喘大鼠氣道炎癥、氣道反應(yīng)性以及血清總IgE水平的影響目的:探討煙曲霉孢子霧化吸入對哮喘模型大鼠氣道內(nèi)嗜酸性炎癥、氣道高反應(yīng)性(airway hyperresponsiveness,AHR)及血清中總IgE水平的影響。方法:將18只Wistar雄性大鼠隨機分為正常組、哮喘組和煙曲霉霧化吸入組。以卵白蛋白注射致敏、霧化激發(fā)的方法構(gòu)建大鼠哮喘模型。煙曲霉暴露組在哮喘模型構(gòu)建成功后,反復(fù)給予煙曲霉霧化吸入。測定每組大鼠對Mch(methacholine,乙酰甲膽堿)的氣道反應(yīng)性,之后采集肺組織與血液標本,測定氣道內(nèi)炎癥以及血清總IgE水平的變化情況。結(jié)果:煙曲霉孢子暴露進一步加重了哮喘大鼠氣道炎癥及氣道高反應(yīng)性(Mch在12.5、25及50 mg/ml濃度下P值均小于0.05),血清總IgE水平也有顯著的提升(P0.05)。各組大鼠血IgE水平與氣道反應(yīng)性指標PC100(將Penh值升高到基礎(chǔ)水平2倍時的Mch濃度定為PC100)密切相關(guān)(r=-0.873,P0.01);同時與BALF內(nèi)炎性細胞中嗜酸粒細胞的百分比也呈現(xiàn)明顯的相關(guān)性(r=0.937,P0.01)。結(jié)論:反復(fù)的煙曲霉菌孢子霧化吸入能夠促進哮喘模型大鼠肺組織內(nèi)嗜酸粒細胞浸潤及氣道高反應(yīng)性的惡化,而嗜酸粒細胞炎癥及氣道高反應(yīng)性的加重可能與血清總IgE水平的升高密切相關(guān)。第二章糖皮質(zhì)激素受體水平變化在煙曲霉菌孢子加重哮喘中的作用目的:煙曲霉菌是否能夠影響哮喘大鼠肺組織內(nèi)GR(糖皮質(zhì)激素受體)水平,從而導(dǎo)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煙曲霉菌對大鼠肺組織內(nèi)GR表達情況的影響。方法:構(gòu)建經(jīng)典的OVA誘導(dǎo)的大鼠哮喘模型,之后進行慢性煙曲霉菌孢子的霧化吸入。觀察曲霉菌孢子霧化吸入后哮喘大鼠氣道炎癥以及氣道高反應(yīng)性的變化情況;通過實時熒光定量PCR以及蛋白免疫印記的方法測得GR受體水平變化。結(jié)果:反復(fù)煙曲霉菌孢子吸入能夠顯著促進OVA哮喘大鼠肺組織氣道炎癥以及氣道高反應(yīng)性的加重(P0.05);并且,在哮喘模型的基礎(chǔ)上吸入煙曲霉菌孢子,肺組織內(nèi)GR受體出現(xiàn)了明顯下調(diào)(P0.05)。結(jié)論:煙曲霉菌孢子吸入能夠誘導(dǎo)哮喘大鼠肺組織內(nèi)GR受體水平的下調(diào),這可能是引起哮喘癥狀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.
【學位授予單位】：上海交通大學
【學位級別】：碩士
【學位授予年份】：2015
【分類號】：R562.25

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