吸入烟曲霉孢子对哮喘大鼠气道上皮重构和MUC5AC表达的影响

Effects of inhalations of Aspergillus fumigatus spores on airway epithelium remodeling and expression of MUC5AC in rats with asthma

目的研究吸入烟曲霉孢子(A f)对哮喘大鼠气道上皮重构和黏蛋白5AC(MUC5AC)表达的影响。方法64只雄性W istar大鼠随机分为正常对照组(A)、慢性哮喘模型组(B)、慢性哮喘+A f孢子吸入组(C)、慢性哮喘+生理盐水吸入组(D)。C、D两组又分为吸入1周、3周和5周组(C1、C3、C5和D1、D3、D5组),每组8只。测定肺泡灌洗液(BALF)中Il-4和IFN-γ水平、气道阻力变化率、杯状细胞增生程度、气道上皮细胞MUC5AC和肺组织MUC5AC mRNA的水平。结果C组BALF中IL-4水平、杯状细胞面积与上皮细胞面积比值、气道阻力变化率、气道上皮细胞MUC5AC表达及肺组织MUC5AC mRNA水平在不同时间点均高于B组和D1、D3、D5组(P<0.05),且C1、C3、C5三组间比较差异有统计学意义(P<0.05);MUC5AC的表达强度与杯状细胞面积/上皮细胞面积比值正相关(r=0.757,P<0.01),与气道阻力变化率正相关(r=0.521,P<0.05)。结论反复吸入A f孢子可上调哮喘大鼠气道MUC5AC的表达,促进杯状细胞增生,增加气道阻力和气道反应性。

Objective To explore the effects of prolonged inhalation of Aspergillus fumigatus （Af） spores on airway epithelium remodeling and expression of mucin5AC（MUC5AC） in rats with asthma. Methods Sixty-four mate Wistar rats were randomly divided into normal control group （group A）, chronic asthma model group （group B）, chronic asthma plus Af spores inhalation group （ group C） and chronic asthma plus saline inhalation group （ group D）. According to the duration of inhalation, group C and D were subdivided into 1 week group （ C1, D1 ） , 3 weeks group （ C3, D3 ） and 5 weeks group （C5, D5） （n = 8 for each group）. The concentrations of I1-4 and IFN-3, in bronchoalveolar lavage fluid （BALF） , the change rate of airway resistance after acetylcholine chloride provocation, the extent of airway goblet cell hyperplasia, the expression of MUC5AC in airway epithelial cells and the level of MUC5AC mRNA in lung tissues were measured. Results The concentration of IL-4 in BALF, the ratio of goblet cell area to epithelial cell area, the change rate of airway resistance after acetylcholine chloride provocation, the MUC5AC expression levels in airway epithelial cells, and the MUC5AC mRNA levels in lung tissues in group C were higher than those in group B, group D~, D3 and Ds at different time points （P 〈 0.05） , and there were significant differences among group C~, C3 and Cs （P 〈 0.05）. The expression intensity of MUC5AC was positively correlated with the ratio of goblet cell area to epithelial cell area （r =0. 757, P 〈0.01） and the change rate of airway resistance （ r = 0. 521, P 〈 O. 05 ）. Conclusion Prolonged inhalation of Aspergillus fumigatus spores can dynamically upregulate the expression of MUC5AC and aggravate airway epithelium remodeling, thus increase the airway sensitivity in rats with chronic asthma.