木瓜蛋白酶诱导的"皮炎→气道炎症"过敏进程小鼠模型OA

Objective An atopic march murine model was established by papain and calcipotriol(MC903),providing a reference for research using allergic airway inflammation murine models.Methods The model was established by percutaneous sensitization with MC903 and papain,followed by papain intranasal challenge to induce airway inflammation.The model was evaluated through skin and lung tissue histopathology,quantitative expression of immuno-inflammatory molecules,and inflammatory cell counting in bronchoalveolar lavage fluid(BALF)and lung tissues.Transcriptome lung tissue immune cell sequencing and functional analysis of differentially expressed genes were performed.Results The ear skin of mice in the atopic march model group was significantly thickened compared with the control group;histopathological examination showed acanthosis and mast cell infiltration,and interleukin(IL)-4 expression was significantly upregulated(P<0.01).Significant peribronchial inflammatory cell infiltration and increased mucus secretion by bronchial epithelial goblet cells were observed in the lung tissue of atopic march model mice(P<0.001).Eosinophil and neutrophil numbers in BALF and lung tissue were significantly increased(P<0.01,P<0.001),and IL-4 and IL-17A cytokine expression in lung tissue were significantly upregulated(P<0.001,P<0.05).Lung tissue immune cell transcriptome sequencing indicated that pathways such as eosinophil and neutrophil chemotaxis,and inflammatory response were significantly activated in atopic march model.Conclusions Percutaneous MC903 and papain sensitization followed by intranasal papain challenge induced a murine atopic march model dominated by T helper 2 and 17 airway inflammation.This model exhibited an airway inflammation phenotype with mixed infiltration of eosinophils and neutrophils,providing a new animal model for the study of mixed granulocytic asthma.