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为研究γ-促分泌酶抑制剂阻断Notch信号对毛细支气管炎(简称毛支)模型大鼠气道炎症反应的影响,建立毛支大鼠模型并且尾静脉注射γ-促分泌酶抑制剂(MW167)。采用HE染色法观察肺组织病理改变,ELISA方法检测血浆中IL-4、INF-γ的水平,real-time PCR检测肺组织和外周血单个核细胞中IL-4mRNA、IFN-γmRNA的表达,Western blotting检测肺组织中NICD、GATA-3、T-bet的蛋白表达。结果显示,MW167注射组较RSV毛支组病理学改变有所减轻;MW167注射组血浆中IL-4水平较RSV组降低,IFN-γ水平增高;肺组织及外周血单个核细胞IL-4mRNA在MW167注射组表达减弱,IFN-γmRNA表达增强;Notch信号和GATA-3表达降低,T-bet表达增强。以上结果提示静脉注射γ-促分泌酶抑制剂能够抑制毛支模型大鼠的气道炎症,可能对毛支有潜在的治疗价值。
In order to study the effect of γ-secretase inhibitor blocking Notch signaling on the airway inflammation in rats with bronchiolitis (abbreviated as branch of hair), a rat model of bronchiolitis was established and injected with γ-secretase inhibitor MW167). The pathological changes of lung tissue were observed by HE staining. The levels of IL-4 and INF-γ in plasma were detected by ELISA. The expression of IL-4 mRNA and IFN-γ mRNA in lung and peripheral blood mononuclear cells were detected by real-time PCR. blotting was used to detect the protein expression of NICD, GATA-3 and T-bet in lung tissue. The results showed that the pathological changes of the MW167 injection group were alleviated compared with the RSV capillary branch group. The plasma level of IL-4 in the MW167 injection group was lower than that in the RSV group and the level of IFN-γ was increased. IL-4 mRNA in lung tissue and peripheral blood mononuclear cells The expression of IFN-γmRNA in MW167-injected group was weakened, the expression of Notch signal and GATA-3 was decreased, and the expression of T-bet was enhanced. These results suggest that intravenous γ-secretase inhibitor can inhibit the bronchial artery airway inflammation in rats, may have a potential therapeutic value on the hair branch.