Notch信号途径对过敏性鼻炎小鼠Treg/Th17细胞免疫失衡调节的机制  

Regulation Mechanism of Notch Signaling Pathway on Immune Imbalance of Treg/Th17 cells in Mice with Allergic Rhinitis

作　　者：廖东 付明亮[1] 高小丹 雷铮 曾颖 窦艳玲 罗利琴 LIAO Dong;FU Mingliang;GAO Xiaodan;LEI Zheng;ZENG Ying;DOU Yanling;LUO Liqin(Department of Otolaryngology,Head and Neck Surgery,Air Force Hospital,Western Theater of the Chinese People's Liberation Army,Chengdu 610000,China)

机构地区：[1]中国人民解放军西部战区空军医院耳鼻喉头颈外科,四川成都610000

出　　处：《贵州医科大学学报》2020年第10期1176-1181,1186,共7页Journal of Guizhou Medical University

基　　金：四川省医学科研课题(S15006)。

摘　　要：目的:探究Notch信号途径对过敏性鼻炎小鼠调节性T细胞/辅助性T细胞17(Treg/Th17)细胞免疫失衡的调节机制。方法:30只BALB/c小鼠均分为对照组、模型组及Notch信号途径抑制剂分泌酶抑制剂(γ-DAPT)组,模型组和γ-DAPT组于第1、7、14及第21~27天采用卵清蛋白(OVA)+氢氧化铝[AL(OH)3]滴鼻诱导过敏性鼻炎,γ-DAPT组在刺激前30 min鼻内滴注20μLγ-DAPT(10μg);末次局部刺激后,流式细胞仪检测各组小鼠鼻黏膜组织Treg及Th17细胞比例,酶联免疫吸附法(ELISA)检测血清白细胞介素(IL-10、IL-17)和转化生长因子β(TGF-β)水平,实时荧光定量PCR和蛋白印迹(Western blot)法检测鼻黏膜组织中Notch1、配体分子Jagged1及下游产物Hes1的表达。结果:与对照组比较,模型组小鼠行为学评分、Th17细胞比例及血清IL-17水平明显升高,鼻黏膜组织Notch1、Jagged1及下游Hes1 mRNA及蛋白表达上调,Treg细胞比例及血清IL-10、TGF-β水平降低(P<0.05);与模型组比较,γ-DAPT组行为学评分、Th17细胞比例及血清IL-17水平明显降低,鼻黏膜组织Notch1、Jagged1及下游Hes1 mRNA及蛋白表达下调,Treg细胞比例及血清IL-10、TGF-β水平升高(P<0.05)。结论:Notch信号途径可能参与过敏性鼻炎的致病机制,其抑制剂γ-DAPT可纠正Treg/Th17细胞免疫失衡,从而减轻过敏性鼻炎症状。Objective:To investigate the regulation mechanism of Notch signaling pathway on immune imbalance of T cells/helper T cells 17(Treg/Th17)cells in mice with allergic rhinitis.Methods:30 BALB/c mice were randomly divided into control group,model group and Notch signaling pathway inhibitor secretase inhibitor(γ-DAPT)group.In model group andγ-DAPT group,allergic rhinitis was induced by ovalbumin(OVA)and aluminum hydroxide[AL(OH)3].Theγ-DAPT group was given intranasal instillation ofγ-DAPT(10 g/20 L)30 min before experiment.The proportion of Treg/Th17 cells in nasal mucosa tissues was detected by flow cytometry in all groups.The levels of serum interleukins(IL-10,IL-17)and transforming growth factorβ(TGF-β)were detected by enzyme-linked immunosorbent assay(ELISA).The expression of Notch1,ligand molecule Jagged1 and downstream product Hes1 in nasal mucosa tissues was detected by real-time fluorescent quantitative PCR and Western blot.Results:Compared with control group,behavior score,proportion of Th17 cells and level of serum IL-17 in model group were significantly increased;expression of Notch1,Jagged1 and downstream Hes1 mRNA and protein in nasal mucosa tissues was up-regulated;proportion of Treg cells,levels of serum IL-10 and TGF-βwere decreased in model group(P<0.05).Compared with model group,behavior score,proportion of Th17 cells and level of serum IL-17 were significantly decreased inγ-DAPT group;expression of Notch1,Jagged1 and downstream Hes1 mRNA and protein in nasal mucosa tissues was down-regulated,proportion of Treg cells,levels of serum IL-10 and TGF-βwere increased inγ-DAPT group(P<0.05).Conclusion:Notch signaling pathway may be involved in the pathogenesis of allergic rhinitis.Its inhibitorγ-DAPT can correct the immune imbalance of Treg/Th17 cells,thereby alleviating the symptoms of allergic rhinitis.

关 键 词：小鼠 NOTCH信号途径 Γ-分泌酶抑制剂 过敏性鼻炎 调节性T细胞 辅助性T细胞17 免疫失衡 

分 类 号：R765.1[医药卫生—耳鼻咽喉科]