烟曲霉菌对糖皮质激素和β2-肾上腺激素受体在哮喘大鼠模型中表达的影响

2018/01/08

   摘要
   目的:传统的吸入型糖皮质激素或β2-肾上腺素受体激动剂在一些哮喘患者中效果不佳,而经验性抗真菌治疗对患者有明显的影响。 本研究旨在探讨短期接触烟曲霉是否能降低哮喘大鼠肺组织中糖皮质激素受体(GCR)和β2-肾上腺素能受体(ADRB2)的表达。
   材料和方法:首先通过卵白蛋白致敏和激发建立慢性哮喘大鼠模型。 然后将慢性哮喘大鼠暴露于短期应用烟曲霉孢子的措施中。 计数这些实验动物中的气道高反应性,支气管肺泡灌洗(BAL)液中的嗜酸性粒细胞比率和血清中的总IgE。 检测并分析肺中GCR和ADRB2的表达。 同时测量肺组织中的Toll样受体(TLR)2,3和4的水平。
   结果:短期接触烟曲霉可降低GCR的表达,加重气道高反应性,增加哮喘大鼠TLR2水平。 暴露于烟曲霉菌后哮喘大鼠ADRB2的表达水平,嗜酸性粒细胞,总IgE,TLR3和TLR4水平无明显变化。
   结论:这些发现表明,烟曲霉暴露可能通过下调哮喘患者GCR的表达而参与糖皮质激素的无应答反应。 对类固醇类耐药的哮喘患者不应忽视烟曲霉菌定植或感染的可能性。

 
                        (中日友好医院呼吸与危重症医学科 张鑫  摘译 林江涛 审校)
 (Exp Lung Res. 2017 May -Jun;43(4-5):197-207.doi:10.1080/01902148.2017.1339142. Epub 2017 Jul 11)
 
 
 
Effects of Aspergillus fumigatus on glucocorticoid receptor and β2-adrenergic receptor expression in a rat model of asthma
 
Zhou X, Dang YJ, Wang GF, Jin XQ.
 

Abstract

PURPOSE:Conventional inhaled corticosteroids or β2-adrenergic receptor agonists do not work well in some asthmatic populations while empirical antifungal therapy has obvious impact on those patients. The study was designed to investigate whether short-term exposure to Aspergillus fumigatus (A. fumigatus) could decrease glucocorticoid receptor (GCR) and β2-adrenergic receptor (ADRB2) expression in lung tissue of asthmatic rats.

MATERIALS AND METHODS:A rat model of chronic asthma was first established by ovalbumin sensitization and challenge. Rats with chronic asthma were then exposed to short-term application of A. fumigatus spores. Airway hyper-responsiveness, eosinophil ratio in bronchoalveolar lavage (BAL) fluid and total IgE in serum were counted in these experimental animals. GCR and ADRB2 expression in the lung were detected and analyzed. Furthermore, the levels of toll-like receptors (TLRs) 2, 3 and 4 in lung tissue were measured.

RESULTS:Short-term exposure to A. fumigatus could down-regulate the expression of GCR, aggravate airway hyper-responsiveness and increase the level of TLR2 in rats with asthma. There were no obvious changes in the levels of ADRB2 expression, recruited eosinophils, total IgE, TLR3 and TLR4 after application of A. fumigatus in asthmatic rats.

CONCLUSIONS:These findings indicate that A. fumigatus exposure may be involved in glucocorticoids unresponsiveness by down-regulating the expression of GCR in asthmatics. The possibility of A. fumigatus colonization or infection should not be ignored in patients of steroid-resistant asthma.


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