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慢性经鼻给予烟曲霉菌孢子会导致哮喘大鼠气道炎症和重塑加重。

Chronic intranasal administration of Aspergillus fumigatus spores leads to aggravation of airway inflammation and remodelling in asthmatic rats.

作者信息

Gao Fu-Sheng, Qiao Jian-Ou, Zhang Yi, Jin Xian-Qiao

机构信息

Department of Respiratory Medicine, First People's Hospital Affiliated to Shanghai Jiao Tong University, Shanghai, China.

出版信息

Respirology. 2009 Apr;14(3):360-70. doi: 10.1111/j.1440-1843.2009.01482.x. Epub 2009 Feb 4.

Abstract

BACKGROUND AND OBJECTIVE

Epidemiological evidence indicates a close link between exposure to fungi and deterioration of asthma. However, the role of fungi as an exogenous precipitant for initiation and progression of asthma has been incompletely explored. In this study, the effects of Aspergillus fumigatus exposure on airway inflammation and remodelling in a rat model of chronic asthma were investigated.

METHODS

The rat model of chronic asthma was established by systemic sensitization and repeated challenge with ovalbumin (OVA). The asthmatic rats were exposed to chronic intranasal inhalation of A. fumigatus spores. Changes in airway inflammation, remodelling and BHR were measured after exposure to the fungus.

RESULTS

Chronic inhalation of A. fumigatus spores elevated the production of T helper 2 (Th2) cytokines, increased the concentration of total serum IgE, and resulted in the recruitment of eosinophils and lymphocyte infiltration into the airways of asthmatic rats. Goblet cell hyperplasia, mucus hyperproduction and subepithelial collagen deposition were also induced by inhalation of the fungus. The remodelling changes induced by inhalation of the fungus paralleled the changes in BHR in this rat model of asthma.

CONCLUSIONS

Chronic exposure to A. fumigatus aggravated Th2 airway inflammation, promoted airway remodelling and increased BHR in OVA-sensitized and -challenged rats.

摘要

背景与目的

流行病学证据表明,接触真菌与哮喘病情恶化之间存在密切联系。然而,真菌作为哮喘发病和进展的外源性诱发因素的作用尚未得到充分研究。在本研究中,我们调查了烟曲霉暴露对慢性哮喘大鼠模型气道炎症和重塑的影响。

方法

通过对卵清蛋白(OVA)进行全身致敏和反复激发建立慢性哮喘大鼠模型。对哮喘大鼠进行慢性鼻内吸入烟曲霉菌孢子处理。在接触真菌后,测量气道炎症、重塑和气道高反应性(BHR)的变化。

结果

慢性吸入烟曲霉菌孢子提高了辅助性T细胞2(Th2)细胞因子的产生,增加了血清总IgE浓度,并导致嗜酸性粒细胞募集和淋巴细胞浸润到哮喘大鼠的气道中。吸入真菌还诱导了杯状细胞增生、黏液过度产生和上皮下胶原沉积。在该哮喘大鼠模型中,吸入真菌引起的重塑变化与BHR的变化相似。

结论

在OVA致敏和激发的大鼠中,慢性暴露于烟曲霉会加重Th2气道炎症,促进气道重塑并增加BHR。

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