哮喘易感基因ORMDL3在哮喘小鼠中的表达及地塞米松的干预作用

The expression of ORMDL3 in murine asthma model and the effect of dexamethasone

目的:探讨哮喘易感基因ORMDL3在支气管哮喘发病时的表达及地塞米松的干预作用。方法:将30只健康清洁级雌性Balb/c小鼠随机分为3组:对照组、哮喘组(卵蛋白致敏)、地塞米松组(卵蛋白致敏,激发前腹腔注射地塞米松1 mg/kg进行干预),每组10只。称量和观察小鼠的体重增长趋势,对小鼠肺组织进行HE染色评价浸润情况,计数3组小鼠的外周血嗜酸性粒细胞,ELISA法检测对比3组小鼠血清白介素4(IL-4)的浓度变化,采用反转录-聚合酶链反应(RT-PCR)方法检测小鼠肺组织ORMDL3 mRNA水平表达。结果:哮喘组小鼠体重增长显著落后于其他两组(P<0.05),地塞米松干预后能缓解生长迟滞,但仍低于对照组(P<0.05)。病理组织学显示哮喘组小鼠肺组织见大量嗜酸性粒细胞浸润,黏膜下层和平滑肌增厚,管腔狭窄,地塞米松组小鼠肺组织改变较哮喘组为轻。哮喘组外周血嗜酸性粒细胞计数显著高于对照组和地塞米松组(P<0.05),地塞米松组计数高于对照组(P<0.05)。哮喘组小鼠的IL-4水平显著高于对照组(P<0.05),经地塞米松干预后IL-4水平显著降低(P<0.05),但仍高于对照组。哮喘组小鼠ORMDL3 mRNA的表达水平较对照组显著升高,地塞米松组小鼠ORMDL3 mRNA水平较哮喘组下降,但未达统计学意义(P>0.05)。结论:卵清蛋白小鼠哮喘模型中ORMDL3的mRNA表达显著增高,地塞米松可下调ORMDL3的表达,但未达到统计学意义,其中的机制有待进一步的深入研究。

Objective：To investigate the role of ORMDL3 in development of bronchial asthma and its response to treatment with dexamethasone.Methods：A total of 30 Balb/c female mice were randomly divided into three groups： control group,untreated asthma group,and dexamethasone-treated group,and 10 mice in each group.The body weight was observed every week and HE-stained was used to observe the changes of pulmonary histopathology.The number of eosnophils（EOS） in peripheral blood of three groups was counted under microscope.The concentration of interlukin-4（IL-4） was determined by ELISA and the expression of ORMDL3 mRNA in lungs was detected by semi-quantitative RT-PCR.Results：Weight gain of asthma group was significantly lower than the other two groups（P〈0.05）,and dexamethasone intervention alleviated the physical retardation,but still lower than the control group（P〈0.05）.There were mass inflammatory cells infiltration in asthmatic group.Dexamethasone ameliorated the above mentioned symptoms significantly.The number of EOS which in treated in untreated asthma group were significantly higher than those in the other two groups（P〈0.05）,and group were higher than those in control group（P〈0.05）.IL-4 was increased after challenged by OVA compared to the control group（P〈0.05）,and it was lower after treated by dexamethasone（P〈0.05）.After challenge,the expression of ORMDL3 mRNA was a significantly elevated in untreated asthma group,and was alleviated in dexamethasone-treated group（P〈0.05）,which was still higher than the control group.Conclusion：Over-expression of ORMDL3 was demonstrated in the mouse airways with asthma,and dexmathesone may be effective as an anti-inflammatory agent by inhibiting ORMDL3 expression.