Study on mechanism of Shema Zhichuan Liquid for improving airway remodeling by inhibiting airway epithelial cell EMT in asthma through NF-κB/VEGFA signaling pathway
Objective:To investigate the effects of Shema Zhichuan Liquid on epithelial-mesenchymal transition(EMT)and airway remodeling in asthmatic mice and its potential mechanisms.Methods:Thirty SPF-grade female mice were randomly divided into control group,model group,low-dose and high-dose Shema Zhichuan Liquid groups,and Dexamethasone group.House dust mite nasal drop sensitization was used to establish an asthma mouse model.The total number of white cells in bronchoalveolar lavage fluid(BALF)was counted by cell counter,the histopathological morphology of mouse lung was observed by HE,PAS and Masson staining,serum inflammatory factors and total IgE were detected by ELISA,and the mRNA expression level of airway remodeling-related indexes was detected by Real-Time PCR.Immunohistochemistry and fluorescence were used to detecte the expression of EMT markers in airway epithelial cells of lung tissues,and Network pharmacology was applied to predict the mechanism of Shema Zhichuan Liquid improving airway remodeling in asthma.Lastly,the expression level of key proteins of p-p65,p-IκB α,TNF-α,and VEGFA were detected by Western Blot.Results:Compared with the model group,the total number of white cell in the alveolar lavage fluid of mice in the low-dose and high-dose groups of Shema Zhichuan Liquid and the Dexamethasone group was significantly reduced(P＜0.01,P＜0.05),the levels of serum IL-4,IL-5,and total IgE were significantly reduced(P＜0.01,P＜0.05),and the pathologies such as the infiltration of inflammatory cells in the lung tissues,the secretion of mucus,and the deposition of collagen were significantly improved(P＜0.01).The expression levels of Muc5ac,Fn1 and α-SMA mRNA,which were related the remodeling of the airways,were reduced(P＜0.01,P＜0.05),and the expression levels of E-Cadherin and ZO-1 proteins in lung tissues were elevated,whereas the proteins of N-Cadherin,α-SMA,p-p65,p-IκB α,TNF-α,and VEGFA were significantly reduced.Conclusion:Shema Zhichuan Liquid can inhibit airway epithelial cell EMT through NF-κB/VEGFA signaling pathway,and then improve asthma airway remodeling.
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