贵州医科大学学报

2020, v.45;No.241(10) 1176-1181+1186

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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

廖东;付明亮;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;

摘要(Abstract):

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 and γ-DAPT group,allergic rhinitis was induced by ovalbumin( OVA) and aluminum hydroxide [AL( OH)3]. The γ-DAPT group was given intranasal instillation of γ-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 factor β( 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-β were 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 in γ-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-β were increased in γ-DAPT group( P < 0. 05). Conclusion: Notch signaling pathway may be involved in the pathogenesis of allergic rhinitis. Its inhibitor γ-DAPT can correct the immune imbalance of Treg/Th17 cells,thereby alleviating the symptoms of allergic rhinitis.

关键词(KeyWords): 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
mice;notch signaling pathway;γ-secretase inhibitor;allergic rhinitis;regulatory T cell(Treg);helper T cell(Th17);immune imbalance

Abstract:

Keywords:

基金项目(Foundation): 四川省医学科研课题(S15006)

作者(Author): 廖东;付明亮;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;

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DOI: 10.19367/j.cnki.2096-8388.2020.10.010

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