γ-分泌酶抑制剂DAPT对哮喘小鼠气道炎症的调控作用分析

辛娜，李敬梅，王永峰，陈婕，王瑶

（西安医学院第一附属医院检验科，陕西 西安，710077）

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摘要：

目的 探究γ-分泌酶抑制剂（DAPT）对哮喘小鼠气道炎症的调控作用。方法 选择健康C57BL/6雌性小鼠120只，随机分成4组，每组30只，分别为健康对照组、哮喘模型组、二甲基亚砜（DMOS）溶剂对照组、DAPT组。除健康对照组，剩余3组小鼠创建哮喘模型。DAPT组在末次激发前0.5 h 经气道使用DAPT，DMSO溶剂对照组给予相同体积的DMSO，健康对照组给予相同体积的生理盐水，哮喘模型组不给予任何处理。末次激发1 d 后，脱颈法处死所有小鼠，收集气道内灌洗液（BALF），测定BALF 内Th1/2 细胞因子变化情况，对BALF 中各种炎性细胞进行计数。结果 健康对照组、哮喘模型组、DMOS溶剂对照 组和DAPT 组小鼠BALF内的IL-4 和IFN-γ水平，白细胞总数、淋巴细胞计数、嗜酸性粒细胞计数比较，差异均有统计学意 义（P<0.05）。结论 DAPT可一定程度纠正哮喘小鼠的免疫偏倚现象，减少肺组织炎性细胞浸润比例，是治疗哮喘的新药物，
值得进一步深入研究。

关键词：支气管哮喘；γ-分泌酶抑制剂；Notch 信号通路

中图分类号：R562文献标志码：A文章编号：2096-1413(2017)20-0004-02

Regulatory effect of γ-secretase inhibitor DAPT on airway inflammation in asthmatic mice
XIN Na, LI Jing-mei, WANG Yong-feng, CHEN Jie, WANG Yao
（Department of Clinical Laboratory, the First Affiliated Hospital of Xi``an Medical University, Xi``an 710077, China）

ABSTRACT: Objective To explore the regulatory effect of γ -secretase inhibitor (DAPT) on airway inflammation in asthmatic mice. Methods A total of 120 health C57BL/6 female mice were selected and divided into healthy control group, asthma model group, DMOS (two methyl sulfoxide) solvent control group and DAPT (γ -secretory enzyme inhibitor) group, with 30 cases in each group. In addition to the healthy control group, mice in the remaining three groups were sensitized to establish asthma model. The DAPT group was given DAPT via airway at 0.5 h before the final excitation, and the DMSO solvent control group was given the same volume of DMSO, the healthy control group was given the same volume of normal saline, and the asthmatic model group was not given any treatment. After 1 day of the final stimulation, all mice were killed by the method of removing neck. The airway lavage fluid (BALF) was collected, and the changes of Th1/2 cytokines and inflammatory cells in the BALF were measured. Results There were significant differences in the levels of IL-4 and IFN-γ, white blood cell count, lymphocyte count and eosinophil count in BALF between healthy control group, asthma model group, DMOS solvent control group and DAPT group (P<0.05). Conclusion DAPT can correct the immune bias of asthmatic mice to a certain extent, and reduce the percentage of inflammatory cell infiltration in lung tissue. It is a new drug for asthma and is worthy of further research.
KEYWORDS: bronchial asthma; γ-secretase inhibitors; Notch signaling pathway

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