Objective:To explore the effect of microRNA(miR-223-3p)on nasal inflammation induced by house dust mite(HDM)in mice with allergic rhinitis(AR)and its related mechanism.Methods:Eighty BALB/c mice were randomly divided into control group,HDM-induced AR group(AR group),miR-223-3p agonist group(agomiR-223-3p group),miR-223-3p inhibitor group(antagomiR-223-3p group)and miR-223-3p agonist+Notch1 knockdown group(agomiR-223-3p+sh-Notch1 group),16 mice in each group.HDM allergen extract was used to construct AR mice model,and miR-223-3p agonist(miR-223-3p agomir),miR-223-3p inhibitor(miR-223-3p antagomir)and adeno-associated virus of knockdown Notch1(AAV-sh-Notch1)nasal administration were used for treatment.After the last stimulation,AR symptom of mice was performed.Serum,nasal lavage fluid(NALF)and nasal mucosal specimens were collected.HE staining was used to detect nasal mucosal damage.Diff Quik staining was used to detect the number of eosinophils in NALF.ELISA was used to detect HDM specific IgE(HDM-sIgE)level in serum and inflammatory factors levels in NALF.RT-qPCR was used to detect miR-223-3p,inflammatory fac-tors and Notch pathway related mRNA levels in nasal mucosa.Western blot was used to detect Notch1 and Jagged1 protein levels in nasal mucosa.Results:Compared with the control group,the nasal itchiness,sneezing and runny nose of mice in AR group were serious,and the nasal mucosa was thickened and a large number of inflammatory infiltrates could be seen.AR symptom score,serum HDM-sIgE level and nasal mucosa miR-223-3p level were increased.In NALF,eosinophils increased,interleukin(IL)-4,IL-5 and IL-13 levels increased,and IL-12 and interferon-y(IFN-y)levels decreased.The levels of IL-4,IL-5 and IL-13 mRNA,Notch1 and Jagged1 mRNA and protein in nasal mucosa were increased,while the levels of IL-12 and IFN-γ mRNA were decreased(all P＜0.05).Compared with AR group,agomiR-223-3p group enhanced the above inflammatory response and activated Notch pathway.In antagomiR-223-3p group,the above inflammatory response was alleviated and Notch pathway was blocked(all P＜0.05).Compared with agomiR-223-3p group,Notch down-expression can reverse the activation of miR-223-3p on nasal inflammatory response in AR mice.Conclusion:MiR-223-3p enhances nasal inflammatory response in HDM induced AR mice by ac-tivating the Notch pathway.
国家科技期刊平台
NSTL
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