Objective To explore the effects of γ,-secretase inhibitor(DAPT) on the airway inflammation,the airway hyperactivity and the imbalance of Thl7/Treg in a mouse model of allergic asthma for providing a theoretical basis for the research and development of anti-asthma activity preparations.Methods Forty-five female C57BL/6 mice were randomly divided into 3 groups:control group,asthma group and DAPT group.The pathological changes of lung tissue were analyzed by hematoxylin-eosin staining.Levels of cytokine and inflammatory mediators in bronchoalveolar lavage fluid(BALF) were measured by enzyme-linked immunosorbent assay.The expression of Foxp3 mRNA in spleen was detected by reverse transcription polymerase chain reaction(RT-PCR).Results The airway inflammation and mucus secretion were alleviated in DAPT group compared with asthma group.The contents of IgE,IL-17,IL-I0 and TGF-β1 in asthma group were (695 + 148) ng/ml,(58 + 6) pg/ml,(148 + 12) pg/ml,(18-+ 3) pg/ml,respectively.The contents of IgE,IL-17,IL-10 and TGF-131 in DAPT group were (486 + 152) ng/ml,(27 ± 6) pg/ml,(193 + 17) pg/ml,(33 ± 5) pg/ml,respectively.Compared with asthma group,the levels of IgE and IL-17 were significantly decreased in DAPT group(P ＜ 0.01),the levels of IL-10,TGF-β1 and the expression of Foxp3 mRNA were significantly increased in DAPT group (P ＜ 0.01).Conclusion The γ-secre tase inhibitor DAPT may efiqciently regulate the imbalance of Th17/Treg to balance a mouse asthmatic model.%目的 研究γ-分泌酶抑制剂DAPT对哮喘气道炎症、气道高反应和Th17/Treg失衡的干预作用,为其抗哮喘活性制剂的研究与开发提供理论依据. 方法 6-8周雌性C57 BL/6小鼠45只被随机分为对照组,哮喘组和DAPT组,每组15只苏木精-伊红(HE)染色法观察气道病理改变,酶联免疫吸附法检测小鼠支气管肺泡灌洗液(BALF)中细胞因子和炎性介质的水平,逆转录聚合酶链反应法(RT-PCR)分析脾脏Foxp3 mRNA的表达. 结果 DAPT组较哮喘组气道炎症明显减轻,气道内黏液分泌显著减少.哮喘组IgE、IL-17、IL-10和TGF-β31的含量分别为(695±148) ng/ml,(58±6)pg/ml,(148±12) pg/ml,(18±3)pg/ml;DAPT组IgE、IL-17、IL-10和TGF-β1的含量分别为(486±152) ng/ml,(27±6)pg/ml,(193±17) pg/ml,(33±5) pg/ml.与哮喘组比较,DAPT组气道灌洗液中IL-17、IgE水平显著降低(P＜0.01),IL-10、rGF-β1水平显著增加(P＜0.01),Foxp3 mRNA的表达也显著增加(P＜0.01). 结论 γ-分泌酶抑制剂DAPT具有抗哮喘小鼠Th17/Treg失衡的作用.
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