慢性烟曲霉暴露对支气管哮喘大鼠气道高反应性、气道炎症及气道重构的影响

Effects of chronic Aspergillus fumigatus exposure on bronchial hyperresponsiveness,airway inflammation and remodeling in rats with bronchial asthma

目的探讨慢性烟曲霉暴露对支气管哮喘大鼠气道高反应性、气道炎症和气道重构的影响。方法将56只雄性Wistar大鼠随机分为A组(慢性哮喘组)、B组(慢性哮喘+烟曲霉孢子滴入组)、C组(慢性哮喘+生理盐水滴入组)、D组[卵白蛋白(OVA)致敏+生理盐水激发+生理盐水滴入组]、E组(OVA致敏+生理盐水激发+烟曲霉孢子滴入组),B组再分成B1、B2、B3组(分别吸入烟曲霉1、3、5周),每组各8只。测定大鼠气道阻力(Raw)及乙酰胆碱注射后Raw变化率;ELISA法测定血清中总Ig E和肺泡灌洗液(BALF)中IL-13、IL-5、IFN-γ、TGF-β水平;制作肺组织切片,并行HE染色、过碘酸雪肤(PAS)染色、Masson三色染色和病理图像形态学测定,观察各组气道上皮细胞损伤脱落、杯状细胞增生及上皮下纤维化程度。结果 B3组Raw和BALF中IL-5、IL-13、TGF-β水平及血清总Ig E水平、炎细胞浸润、嗜酸性粒细胞浸、脱落上皮长度/气道上皮内径、杯状细胞增生、上皮下胶原纤维沉积均高于A、C、D、E组(P<0.05或P<0,01)。结论慢性烟曲霉暴露可加重支气管哮喘大鼠气道高反应性、气道炎症和气道重构程度。

Objective To investigate the effects of chronic Aspergillus fumigatus （ A.fumigatus ） exposure on the bronchial hyperresponsiveness , airway inflammation and remodeling in rats with bronchial asthma .Methods Sixty-four male Wistar rats were randomly divided into group A （ chronic asthma group ） , group B （ chronic asthma ＋Af spore inha-lation group）, group C （chronic asthma ＋saline inhalation group）, group D （OVA-sensitized and saline-challenged ＋saline inhalation group ） and group E （ OVA-sensitized and saline-challenged ＋Af spore inhalation group ） .Meanwhile , group B was then divided into groups B1, B2 and B3 （Af spore inhalation for 1 week, 3 weeks and 5 weeks） （n=8）.The airway resistance （ Raw ） and change rate of R aw after administration of acetylcholine chloride were measured by using a com-puterized system.The concentration of total serum IgE and IL-5, IL-13, IFN-γ, TGF-βlevels in the bronchoalveolar lav-age fluid （ BALF） were measured by ELISA .Lung sections were made and then received hematoxylin and eosin （ HE） stai-ning, periodic acid Schiff （ PAS） staining and Masson trichrome staining .The images were analyzed morphometrically to e-valuate the airway epithelial detachment , goblet cell hyperplasia and subepithelial fibrosis in rats of the 7 groups .Results The change rate of R aw after administration of acetylcholine chloride , the IL-5, IL-13, TGF-βlevels, the concentration of total serum IgE, the inflammatory cell infiltration, the eosinophils, the airway epithelial detachment length/epithelial diam-eter, the goblet cell hyperplasia and subepithelial collagen deposition were all higher than those in the groups of A , C, D and E（P〈0.05 or P〈0.01）.Conclusions Chronic Aspergillus fumigatus （A.fumigatus） exposure aggravates the bronchial hyperresponsiveness , airway inflammation and the degree of airway remodeling in rats with bronchial asthma .