慢性烟曲霉暴露对哮喘大鼠气道嗜酸粒细胞性炎症及气道高反应性的影响

The Influence of Chronic Aspergillus fumigatus Exposure on Airway Eosinophilia and Hyperresponsiveness in Rat Asthma Model

目的探讨慢性烟曲霉暴露对哮喘大鼠气道嗜酸粒细胞的募集活化及气道反应性的影响。方法使用卵白蛋白腹腔注射后雾化吸入法制备Wistar大鼠哮喘模型,采用雾化吸入孢子悬液的方式模拟慢性烟曲霉暴露,并设置相应的生理盐水对照组。测定反映大鼠气道反应性的指标Penh值,ELISA法测定支气管肺泡灌洗液(BALF)中白细胞介素5(IL-5)、嗜酸粒细胞趋化因子(Eotaxin)浓度,肺组织切片HE染色观察气道炎症性病理改变,测定嗜酸粒细胞浸润程度。瑞士姬姆萨复合染色计数BALF中嗜酸粒细胞比例。结果烟曲霉可引起哮喘大鼠气道反应性升高及气道嗜酸粒细胞增多,加重哮喘大鼠气道过敏性炎症。烟曲霉暴露组中气道嗜酸性细胞增加与IL-5、Eotaxin水平升高相一致。但烟曲霉对生理盐水对照组大鼠的气道反应性、嗜酸粒细胞及IL-5、Eotaxin水平改变无显著作用。结论烟曲霉孢子雾化吸入可促进IL-5、Eotaxin的生成从而加重哮喘大鼠气道的嗜酸粒细胞性炎症,并可加重气道高反应性。

Objective To explore the effect of Aspergillus fumigatus on airway eosinophilia and hyperresponsiveness in rat model of chronic asthma. Methods Wistar rats were sensitized by intraperitoneal injections with ovalbumin （OVA） followed by chronic inhalation of nebulized OVA or physiologic saline. Rats were administered via the airways with placebo or aerosolized Aspergillus fumigatus spores suspension mimicking chronic Aspergillus fumigatus exposure. The Penh after acetyleholine provocation was detected using WBP system. The concentrations of IL-5 and eotaxin in BALF were measured by ELISA. The extents of eosinophil infiltration were evaluated on hematoxylin and eosin-stained （HE） and Wright-Giemsa stained BALF cells smear. Results AspergiUusfumigatus worsened allergic airway inflammation in OVA-challenged rats,as evidenced by enhanced bronchial responsiveness to inhaled acetylcholine and increased bronchial eosinophilia. Elevated airway eosinophilia corresponded with higher levels of IL-5 and eotaxin in the Aspergillus Fumigatus exposure group. Aspergillus fumigatus, however, did not affect bronchial responses, numbers of eosinophils,IL-5 and eotaxin levels in saline challenged mice. Conclusions The results show that chronic Aspergillus fumigatus exposure aggravates eosinophilic airway inflammation in asthma rats by enhancing IL-5 and eotaxin production. Aspergillus fumigatus also increases bronchial hyperresponsiveness in asthma rats.