摘要
目的研究γ-促分泌酶抑制剂阻断Notch信号对支气管哮喘(简称哮喘)模型小鼠气道炎症反应的影响,为哮喘治疗寻找新的药物提供理论基础。方法制作小鼠哮喘模型,在小鼠激发阶段尾静脉注射γ-促分泌酶抑制剂MW167,采用RT-PCR方法检测小鼠肺T细胞IL-4mRNA及IFN-γmRNA的表达,ELISA方法检测外周血清及BALF上清中IL-4及IFN-γ水平。结果 MW167注射组较哮喘组病理学改变减轻,而肝及肾无明显形态学改变,MW167阻断Notch信号后,MW167注射组小鼠肺T细胞IL-4mRNA的表达较哮喘组减弱,而IFN-γmRNA的表达增强(IL-4:0.119±0.045比0.414±0.214,P<0.01;IFN-γ:0.459±0.205比0.170±0.050,P<0.01);MW167注射组外周血清及BALF中IL-4的表达较哮喘组减弱[血清:(19.601±0.870)ng/L比(26.046±2.211)ng/L,P<0.05;BALF:(75.077±14.438)ng/L比(113.478±8.628)ng/L,P<0.01)];外周血清中及BALF中IFN-γ的表达较对照组增强[血清:(10.644±3.338)ng/L比(5.119±2.230)ng/L,P<0.01];BALF:(26.131±3.608)ng/L比(21.299±2.830)ng/L,P<0.01]。结论静脉注射γ-促分泌酶抑制剂抑制了哮喘模型小鼠气道炎症,对哮喘有潜在的治疗价值。
Objective This study investigated the affection to airway inammation of asthmatic mouse models after blocking Notch signaling by γ-secretase and provide rationale for seeking new target for asthma drug treatment.Methods An OVA-induced asthmatic mouse model was established. γ-secratase inhibitorⅡ（MW167）was injected by vena caudalis at the stimulatory stage. The expression of IL-4 mRNA and IL-4 mRNA in mouse lung T cells was detected by RT-PCR, the level of IL-4 and IFN-γ in peripheral serum and BALF supernatant was done by ELISA.Results The histopathologic change in MW167-treated group was significantly alleviated compared to asthma group, whereas liver and kidney had no dramatic change. The mRNA expression of IL-4 decreased and IFN-γ increased significantly in MW167 intravenous injection group after Notch was blocked by MW167 （IL-4：0.119±0.045 vs 0.414±0.214,P0.01,IFN-γ：0.459±0.205 vs 0.170±0.050, P0.01）.The level of IL-4 in peripheral serum [（19.601±0.870） ng/L vs （26.046±2.211） ng/L, P0.05） and BALF supernatant [（75.077±14.438） ng/L vs （113.478±8.628） ng/L, P0.01] was decreased, while the level of IFN-γ in peripheral serum [（10.644±3.338） ng/L vs （5.119±2.230） ng/L, P0.01] and BALF supernatant [ （26.131±3.608） ng/L vs （21.299±2.830） ng/L, P0.01] was increased in contrasting to asthma group （P0.01 both）.Conclusions γ-secratase inhibitor by intravenous injection suppresses the airway inflammation of asthmatic mouse models and has potential therapeutic value for treating asthma by inhibiting airway infammation.
出处
《中华哮喘杂志（电子版）》
CAS
2012年第1期6-9,共4页
Chinese Journal of Asthma(Electronic Version)
基金
上海市科学技术委员会资助(114119b0800)
