【摘要】 目的 全面评估使用卵清蛋白(OVA)联合曲霉菌蛋白酶(Aspergillus protease，AP)诱导的嗜酸型慢性鼻-鼻窦炎伴鼻息肉(eosinophilic chronic rhinosinusitis with nasal polyps，ECRSwNP)模型中各免疫细胞浸润、上皮屏障功能及嗅神经元损伤等多种免疫学特征改变。方法 使用HE、PAS、Masson染色观察小鼠鼻黏膜息肉样凸起、杯状细胞增生、上皮下胶原沉积等改变，免疫组化染色检测黏膜内多种免疫细胞、嗅神经元改变及上皮紧密连接蛋白的表达。结果 与对照组小鼠相比，OVA联合AP组小鼠鼻黏膜上皮厚度显著增加并有明显息肉样凸起、上皮下胶原沉积、杯状细胞增生。免疫组化染色结果显示OVA联合AP组小鼠鼻黏膜中嗜酸性粒细胞显著增多，中性粒细胞、肥大细胞和CD4~+T细胞数也高于对照组。此外，OVA联合AP组小鼠鼻黏膜上皮紧密连接蛋白ZO-1和E-cadherin的表达和OMP+嗅神经元面积均显著低于对照组。结论持续暴露OVA及AP可成功诱导ECRSwNP模型，为进一步研究其发病机制和评估新的治疗策略提供基础。更多还原

【Abstract】 OBJECTIVE Aimed to comprehensively evaluate various immunological changes in a mouse model of eosinophilic chronic rhinosinusitis with nasal polyps(ECRSwNP) induced by ovalbumin(OVA) combined with Aspergillus protease(AP),including nasal polyps-like lesions,subepithelial collagen deposition,inflammatory cell infiltration,epithelial barrier function,and olfactory neuron damage.METHODS C57BL/6 mice were challenged with OVA and AP for 12 weeks.Hematoxylin-eosin(HE),periodic acid-Schiff(PAS),and Masson staining were used to observe the changes of nasal polyps-like lesions,goblet cell hyperplasia,and subepithelial collagen deposition.Immunohistochemistry staining(IHC) was employed to detect the changes of various inflammatory cells,olfactory neurons,and the expression of epithelial tight junction proteins in the nasal and sinus mucosa.RESULTS Compared to the control group,the OVA and AP group showed significantly increased epithelial thickness,noticeable nasal polyps-like lesions,marked subepithelial collagen deposition,and goblet cell hyperplasia in the nasal and sinus mucosa.IHC results revealed a significant increase in eosinophils,along with higher numbers of neutrophils,mast cells,and CD4~+T cells in the OVA and AP group.Additionally,the expression of tight junction proteins ZO-1 and E-cadherin in the nasal and sinus mucosa and the area of OMP+ olfactory neurons in the olfactory epithelium were significantly lower in the OVA and AP group compared to the control.CONCLUSION Continuous exposure to OVA combined with AP successfully induces ECRSwNP.The establishment of this model provides a foundation for further research into the pathogenesis and the evaluation of new therapeutic strategies for ECRSwNP.更多还原