基于Notch1-Jagged1通路探讨鹿鹅鼻炎方对变应性鼻炎小鼠Th17/Treg的影响OA北大核心CSTPCD

Objective To investigate the effects of Lu'e Rhinitis Formula(LEBY)on Notch1-Jagged1 signaling pathway and helper T cell 17(Th17)/regulatory T cell(Treg)immune imbalance in allergic rhinitis(AR)mice.Methods Thirty BALB/c mice were randomly divided into the sham group,model group,LEBY low,medium,high dose(LEBYL,LEBYM,LEBYH)group,6 in each group.AR mice model was established by inducing ovalbumin(OVA)as the allergen.LEBYL,LEBYM,LEBYH groups were given intragastric administration of LEBY as 0.5,1,2 g/kg per day.The nasal symptoms(sneezing and runny nose)were assessed by behavioral observation in each group.Nasal lavage fluid(NLF)cell count was performed.The morphological changes of nasal mucosa and the numbers of eosinophils,goblet cells and mast cells in each group were assessed.The enzyme-linked immunosorbent assay(ELISA)was used to detect the levels of OVA-specific IgE(OVA-sIgE),OVA-specific IgG(OVA-slgG)in serum,interleukin-10(IL-10)and interleukin-17(IL-17)in NLF.The relative protein expressions of Notch1,Jagged1,and retinoid related orphan receptorγt(ROR γt)and fork head box transcription factor 3(Foxp3)in nasal mucosa were measured by Western Blot.Results Compared with the sham group,significant proliferation and metaplasia of nasal mucosal epithelial cells as well as eosinophils dominating the inflammatory infiltrating cells were observed in the model group,with cilium shedding and submucosal vessels dilatation.After intervention with LEBY,the damage of the mucosal epithelial has been partly restored.Compared with the sham group,the quantities of nasal itching and sneezing 10 min after the last stimulation,the thickness of nasal mucosal epithelium,the quantities of eosinophils,globet cells and mast cells,the levels of serum OVA-sIgE and OVA-sIgG,IL-17 in NLF,and the expression of RORγt,Notch1,and Jagged1 proteins in the nasal mucosa increased(P＜0.05),the level of IL-10 in NLF and the expression of Foxp3 protein in the nasal mucosa decreased in model group(P＜0.05).Compared with the model group,the quantities of nasal itching and sneezing 10 min after the last stimulation,the thickness of nasal mucosal epithelium and the quantities of eosinophils,the levels of serum OVA-sIgE and OVA-sIgG,IL-17 in NLF,and the expression of RORγt,Notch1 and Jagged1 proteins in the nasal mucosa decreased,the expression of Foxp3 proteins in the nasal mucosa increased in LEBYL,LEBYM,LEBYH groups(P＜0.05).The quantities of globet cells and the expression of RORγt protein in the nasal mucosa decreased,the level of IL-10 in NLF increased in LEBYM and LEBYH group(P＜0.05).The mast cells in nasal mucosa decreased in LEBYH group(P＜0.05).Conclusion The mechanism of LEBY intervention in AR mice may be achieved by inhibiting Notch1-Jagged1 expression and regulating Th17/Treg immune homeostasis.