Mechanism Of Glucocorticoids In Promoteing Asthma Epithelial Cell Apoptosis By Regulating Nrf2 Signaling Pathway

Objective: To investigate the underlying molecular mechanism of glucocorticoid inducing epithelial cell apoptosis in asthmatic mice,and to provide a new strategy for the prevention and treatment of its side effect.Methods: 1.Constructing asthma model and treating them with dexamethasone,and using immune-histochemistry and immunefluorescence to detect the expression of nuclear factor erythroid 2-related factor 2(Nrf2)in lung.Western Blot was used to detect the levels of Nrf2 protein and Kelch like ECH associated protein 1(Keap1);2.Human bronchial epithelial cells(16HBE)were treated with House dust mites(HDM),Dexamethasone(DEX)treatment and to detect apoptosis levels under different processing factors.Western Blot,immunofluorescence,and qPCR were used to detect Nrf2 transcription and protein levels in each group.Western Blot detect the changes of heme oxygenase-1(HO-1);3.After the cells were treated with the natural antioxidant Sulforaphane(SFN),the expression of Caspase3 and Nrf2 was detected by Western Blot.Results: Immunohistochemistry and immunofluorescence showed that the expression of Nrf2 in dexamethasone group was significantly reduced compared with asthma(P <0.05),and the results of Western Blot showed that Nrf2 in lung of dexamethasone group was significantly lower than asthma group(P <0.05),Keap1 protein was significantly increased compared with asthma group(P <0.05).2.Apoptosis of 16 HBE cells increased after HDM treatment(P <0.05).Apoptosis of HDM and DEXtreated groups more increased than HDM-treated group(P <0.05).3.DEX can inhibit the mRNA and protein level of Nrf2(P <0.05),and reduce the expression of HO-1(P <0.05)4.Western Blot show that the expression of Nrf2 increased after SFN-treated cells(P <0.05)),The expression of Caspase3 in 16 HBE cells decreased after dexamethasone treatment(P <0.05).Conclusion: DEX can inhibit Nrf2 signaling pathway,leading to airway epithelial apoptosis in asthma increasing.Activation of Nrf2 after SFN treatment can partially reverse this effect of DEX.It is suggested that Nrf2 signaling pathway may play an important role in DEX-induced apoptosis.