酌鄄促分泌酶抑制剂对毛细支气管炎模型大鼠体内Th17细胞分化的影响.PDF

王海英等摇 酌鄄促分泌酶抑制剂对毛细支气管炎模型大鼠体内Th17 细胞分化的影响摇 第12期 ·1765 · doi:10.3969/ j.issn.1000鄄484X.2016.12.008 酌鄄促分泌酶抑制剂对毛细支气管炎模型大鼠体内 Th17 细胞分化的 影响淤 王海英摇 刘良宵摇 吴福玲摇 高摇 萌摇 (滨州医学院,烟台264003) 摇 摇 中图分类号摇 R392鄄33摇 摇 文献标志码摇 A摇 摇 文章编号摇 1000鄄484X(2016)12鄄1765鄄04 [摘摇 要]摇 目的:研究酌鄄促分泌酶抑制剂阻断Notch信号对毛细支气管炎(简称毛支)模型大鼠Th17 细胞发育和分化 的影响,为毛支治疗寻找新的药物提供理论基础。 方法:按随机对照原则将SD大鼠分为正常组、毛支组和酌鄄促分泌酶抑制剂 组,滴鼻法成功建立毛支模型,而后尾静脉注射酌鄄促分泌酶抑制剂MW167,通过HE染色观察肺组织病理改变,ELISA检测血 浆中白介素17(IL鄄17)的水平,实时荧光定量PCR检测肺组织和外周血单个核细胞中ROR酌t mRNA 的表达,Western blot检测 肺组织中Notch信号、ROR酌t 的蛋白表达。 结果:与毛支组相比,MW167组肺组织病理学改变减轻;血浆IL鄄17水平也较毛支 组降低;肺组织及外周血单个核细胞ROR酌t mRNA在MW167注射组表达均减弱;MW167组肺组织Notch信号和ROR酌t蛋白 的表达也显著降低。 结论:静脉注射酌鄄促分泌酶抑制剂能够通过阻断Notch信号通路抑制Th17细胞的分化,缓解毛支模型大 鼠的气道炎症,对毛支有潜在的治疗价值。 [关键词]摇 毛细支气管炎;Notch;酌鄄促分泌酶抑制剂;Th17细胞 Affection todifferentiationof Th17 cellinbronchiolitisratmodelsafterinjecting 酌鄄secretase inhibitor WANGHai鄄Ying,LIULiang鄄Xiao,WUFu鄄Ling,GAOMeng郾BinzhouMedical University,Yantai264003,China [Abstract]摇 Objective:To investigate the affectiontothedifferentiationofTh17 cell inrat modelsof bronchiolitisafterblocking Notch signaling by 酌鄄secretase inhibitor and provide rationale to seek new target for bronchiolitis drug treatment郾Methods:The rats were randomly dividedintonormal group,bronchiolitisgroup and酌鄄secretaseinhibitor group郾Themodel of bronchiolitiswasestablished successfully by nasal dripping,and 酌鄄secretase inhibitor(MW167)was injected into the vena caudalis郾The pathological changes of the airway were observed by HE staining;the plasma level of interleukin17(IL鄄17) was detected by ELISA;the level of ROR酌t mRNA in lung tissues and peripheral blood mononuclear cells(PBMCs) was tested by real鄄time quantitative PCR;the levels of Notch signaling and ROR酌t protein in lung tissues were examined by Western blot郾Results:Compared to the bronchiolitis group,the histopathologic change in MW167 intravenous injection group was significantly alleviated;the plasm