2017 年第 10 期 第 12 卷

γ-促分泌酶抑制剂对呼吸道合胞病毒毛细支气管炎患儿外周血单个核细胞中T-bet的影响

Effect of γ-secretase inhibitor on T-bet in peripheral blood mononuclear cells in children with respiratory syncytial virus bronchiolitis

作者：刘良宵张雪静吴福玲王海英

英文作者：Liu Liangxiao Zhang Xuejing Wu Fuling Wang Haiying

单位：256600滨州医学院附属医院儿科

英文单位：Department of Pediatrics Binzhou Medical University Hospital Shandong Province Binzhou 256600 China

关键词：毛细支气管炎；T-bet；呼吸道合胞病毒；Notch信号通路；γ-促分泌酶抑制剂

英文关键词：Capillarybronchitis;T-bet;Respiratorysyncytialvirus;Notchsignalingpathway;γ-secretinaseinhibitor

• 摘要：

• 目的 研究γ-促分泌酶抑制剂MW167阻断Notch信号通路对呼吸道合胞病毒（RSV）毛细支气管炎患儿外周血单个核细胞（PBMC）中T-bet的影响，为治疗毛细支气管炎提供新的思路。方法 选取2016年9月至2017年3月在滨州医学院附属医院住院的RSV毛细支气管炎患儿30例（毛细支气管炎组）和同期健康体检儿20例（正常对照组）。抽取受检对象外周静脉血，分离PBMC，而后体外刺激培养，按以下方案进行干预：对照组［正常对照组PBMC＋二甲基亚砜（DMSO）］，RSV组（毛细支气管炎组PBMC＋DMSO），MW167组（毛细支气管炎组PBMC＋MW167＋DMSO）。酶联免疫吸附试验法检测细胞培养上清液中γ-干扰素水平；实时荧光定量聚合酶链反应检测PBMC中γ-干扰素和T-bet mRNA的表达水平。结果 与对照组相比，RSV组血浆γ-干扰素水平明显降低［（60±10）mg/L比（112±30）mg/L］（P＜0.05），对照组γ-干扰素和T-bet mRNA相对表达量设为1.00，RSV组γ-干扰素和T-bet mRNA相对表达量［（0.21±0.05）、（0.33±0.15）］明显降低（均P＜0.01）；与RSV组相比，MW167组血浆γ-干扰素水平［（99±10）mg/L］明显升高（P＜0.05），细胞中γ-干扰素和T-bet mRNA相对表达量［（0.81±0.25）、（1.00±0.21）］明显升高（均P＜0.01）。结论 γ-促分泌酶抑制剂能够升高RSV毛细支气管炎患儿的血浆γ-干扰素水平，以及PBMC中γ-干扰素和T-bet mRNA水平。

• Objective To investigate the effect of γ-secretase inhibitor MW167 blocking Notch signaling pathway on T-bet in peripheral blood mononuclear cells（PBMC） in children with respiratory syncytial virus（RSV） bronchiolitis. Methods From September 2016 to March 2017, 30 children with RSV bronchiolitis（bronchiolitis group） and 20 healthy children（normal control group） were enrolled at Binzhou Medical University Hospital. PBMC was separated in normal control group and cultivated with dimethyl sulfoxide（DMSO）; PBMC separated in bronchiolitis group was cultivated with DMSO（RSV group） and MW167＋DMSO（MW167 group） respectively. The level of γ-interferon in culture supernatant fluid was tested by enzyme linked immunosorbent assay; expressions of γ-interferon and T-bet mRNA in PBMC were tested by real-time fluorescent polymerase chain reaction method. Results The plasma level of γ-interferon in RSV group was significantly lower than that in control group［（60±10）mg/L vs （112±30）mg/L］（P＜0.05）; relative expression quantities of γ-interferon and T-bet mRNA in PBMC in RSV group［（0.21±0.05）, （0.33±0.15）］ were significantly lower than those in control group（1.00）（P＜0.01）. The plasma level of γ-interferon in MW167 group［（99±10）mg/L］ was significantly higher than that in RSV group（P＜0.05）; relative expression quantities of γ-interferon and T-bet mRNA in PBMC in MW167 group［（0.81±0.25）, （1.00±0.21）］ were significantly higher than those in RSV group（P＜0.01）. Conclusion γ-secretase inhibitor can increase expressions of γ-interferon and T-bet in PBMC in children with RSV bronchiolitis.