烟曲霉菌损伤鼻上皮功能致慢性鼻窦炎的研究

Aspergillus Fumigatus Damage Nasal Epithelial Barrier Function in Chronic Rhinosinusitis Mice Model

目的建立慢性鼻窦炎(chronic rhinosinusitis,CRS)的小鼠模型,并探讨紧密连接蛋白在烟曲霉菌致慢性鼻窦炎中的作用。方法8周大BALB/c雄鼠10只腹腔致敏及鼻腔滴注烟曲霉菌提取物(鼻窦炎组),建立慢性鼻窦炎的动物模型。10只对照组小鼠腹腔注射及鼻腔滴注等量无菌磷酸盐缓冲液(phosphate buffered saline,PBS)。组织病理学切片检测鼻黏膜组织变化,免疫组化染色比较紧密连接蛋白在两组表达的差异。结果与对照组小鼠比较,鼻窦炎组小鼠鼻黏膜纤毛柱状上皮结构紊乱,呈波浪状改变,杯状细胞增生,黏膜下组织肿胀,伴有炎性粒细胞浸润和腺体增殖,且鼻上皮细胞紧密连接蛋白的表达量明显低于对照组。结论本研究通过腹腔致敏及鼻腔滴注烟曲霉菌提取物的方式建立了慢性鼻窦炎的小鼠模型,烟曲霉菌提取物可能通过破坏鼻上皮间紧密连接蛋白致小鼠鼻腔鼻窦炎症改变。

Objective To develop a mouse model of chronic rhinosinusitis(CRS)and explore the role of tight junctions in CRS caused by Aspergillus fumigatus(Af).Methods Ten male eight-week-old BALB/c mice were sensitized intraperitoneally and received nasal challenges with Af extract in CRS group.Ten control group mice received equal amount of sterile PBS.Hematoxylin-eosin staining(HE),periodic acid-schiff staining(PAS)and toluidine blue dyeing(TB)were used to detect the nasal histopathological changes.The expression of tight junction proteins in the two groups was compared by immunohistochemistry(IHC).Results Compared with the control group,CRS group mice exhibited disordered ciliated columnar epithelial structure,goblet cell proliferation,submucous tissue swelling,inflammatory granulocyte infiltration and gland proliferation.Additionally,significantly lower expression of tight junction proteins was observed in the CRS group,which may contribute to the development of CRS.Conclusion We successfully developed a CRS mouse model by intraperitoneal sensitization and intranasal drip of Af extract.Our research suggested that the Af extract can damage the nasal epithelial barrier function,therefore,promoting the development of CRS in mice.