DAPT对变应性鼻炎小鼠模型及相关细胞因子表达的影响  

Effects of DAPT on allergic rhinitis model and expression of related cytokines in mice

作　　者：夏翠[1] 祝康[1] 郑国玺[1] XIA Cui;ZHU Kang;ZHENG Guoxi(Department of Otolaryngology Head and Neck Surgery,the Second Affiliated Hospital of Medical College,Xi’an Jiaotong University,Xi’an 710004,China)

机构地区：[1]西安交通大学第二附属医院耳鼻咽喉头颈外科病院,陕西西安710004

出　　处：《中国耳鼻咽喉颅底外科杂志》2020年第5期512-516,共5页Chinese Journal of Otorhinolaryngology-skull Base Surgery

基　　金：国家自然科学基金面上项目(81271057)。

摘　　要：目的通过观察γ-促分泌酶抑制剂(GSI)DAPT对变应性鼻炎小鼠鼻中隔黏膜病理学改变、血清IgE表达、Notch信号通路相关基因及Th型细胞因子(IL-4、IFN-γ)的表达变化,来研究DAPT对变应性鼻炎发生发展的影响及其作用机制。方法选取7~8周龄BALB/c小鼠32只,随机分为4组:变应性鼻炎组、DAPT组、对照组及二甲基亚砜(DMSO)组,每组各8只。分析比较不同组小鼠IgE表达水平及鼻腔黏膜病理改变;并检测各组小鼠鼻中隔黏膜Notch相关基因的表达变化、外周血清及鼻腔灌洗液上清中相关细胞因子(IL-4、IFN-γ)的表达量。结果 (1)DAPT处理小鼠后,鼻中隔黏膜的病理损伤与模型组相比有明显改善:炎性细胞浸润逐渐减少,炎症改变明显减轻;(2)DAPT组小鼠血清特异性IgE抗体浓度较模型组明显下降,差异具有统计学意义(P<0.05);(3)RT-PCR结果显示DAPT组小鼠鼻中隔黏膜Notch1、Notch3、Notch4的mRNA表达减少,与模型组相比差异具有统计学意义(P<0.05);相反,Notch2的表达则上升,与模型组相比差异具有统计学意义(P<0.05);(4)细胞因子的检测显示:与模型组小鼠相比,DAPT组小鼠外周血血清及鼻腔盥洗液中IL-4的表达明显降低,差异均具有统计学意义(P<0.05);相反,IFN-γ的表达却升高,与模型组相比差异具有统计学意义(P<0.05)。结论 (1)DAPT能改善小鼠鼻中隔黏膜的病理损伤并减少血清中特异性抗体IgE的表达;(2)能影响Notch信号通路相关基因的转录,促进Th0细胞向Th1方向分化,进一步影响变应性鼻炎的发生发展。Objective To study the effect of gamma-secreta inhibitor(GSI) DAPT on the development of allergic rhinitis(AR) via observing the pathological changes of nasal septum mucosa, the expression of serum IgE, Notch signaling pathway related genes as well as Th cytokines(IL-4, IFN-gamma) in model mice with AR.Methods Thirty-two BALB/c mice aged 7-8 weeks were randomly and equally divided into four groups: AR group, DAPT group, control group and dimethyl sulfoxide(DMSO) group. The pathological changes of nasal mucosa in different groups were observed and compared. The expressions of Notch-related genes in nasal septum mucosa, specific IgE levels in peripheral serum as well as the expressions of cytokines(IL-4, IFN-γ) in peripheral serum and nasal lavage supernatant were detected.Results(1)The pathological damage of nasal septum mucosa in DAPT group was significantly mild compared with that in the AR group.(2)The serum specific IgE antibody concentration in DAPT group was significantly lower than that in the AR group(P<0.05).(3)Reverse transcription-polymerase chain reaction(RT-PCR) results revealed that the mRNA expressions of Notch1, Notch3 and Notch 4 in nasal septum mucosa of the DAPT group were lower than those of the AR group, and the differences were all statistically significant(all P<0.05). On the contrary, the mRNA expression of Notch 2 in nasal septum mucosa of the DAPT group was higher than that of the AR group, and the difference was also statistically significant(P<0.05).(4)Cytokine assay showed reduced expression of IL-4 and increased expression of IFN-γin both peripheral serum and nasal lavage supernatant of the DAPT group compared with the AR group, and the differences were statistically significant(all P<0.05).Conclusions DAPT can improve the pathological damage of nasal septum mucosa and reduce the expression of specific IgE in serum of AR mice. DAPT can affect the transcription of Notch signaling pathway related genes, promote the differentiation of Th0 cells into Th1, and further affect the occurren

关 键 词：变应性鼻炎 NOTCH基因 动物 γ-促分泌酶抑制剂 

分 类 号：R765.21[医药卫生—耳鼻咽喉科]