STAT6和ORMDL3在哮喘小鼠肺组织中的表达及布地奈德的干预作用

Down-regulatory effects of budesonide on expression of STAT6 and ORMDL3 in lung tissues of asthmatic mice

摘要:

目的 探讨信号转导和转录激活因子6（STAT6）以及哮喘易感基因血清类黏蛋白1 样蛋白3（ORMDL3）在哮喘小鼠气道重塑中的作用，并观察布地奈德（BUD）对上述两种物质水平的干预作用。方法 BALB/c 雌性小鼠30 只，随机分为对照组、哮喘组和BUD 组。应用鸡卵清蛋白（OVA）激发试验建立哮喘小鼠模型，BUD 组在每次激发前30 min 应用生理盐水溶解的BUD 雾化液进行雾化吸入，对照组应用生理盐水替代OVA 溶液。苏木精-伊红染色及Masson 染色观察各组小鼠气道病理学改变；ELISA 法检测各组小鼠肺组织匀浆中IL-13 水平；RT-PCR 法检测各组肺组织STAT6 及ORMDL3 的mRNA 表达。结果 哮喘组气道病理学改变较正常组和BUD 组明显，而BUD 组气道病理学变化较哮喘组减轻。哮喘组和BUD 组IL-13 水平、STAT6 及ORMDL3 的mRNA 表达均明显高于对照组（P<0.05），且哮喘组IL-13 水平、STAT6 和ORMDL3 的mRNA 表达均高于BUD 组（P<0.05）。Pearson 相关分析显示STAT6 和ORMDL3 mRNA 在哮喘组的表达呈正相关（r=0.676，P=0.032）。结论 STAT6 和ORMDL3 可能参与了小鼠气道重塑过程，BUD 可能通过下调STAT6和ORMDL3 的mRNA 表达，改善气道重塑。

Abstract:

Objective To investigate the roles of signal transduction and activator of transcription 6 (STAT6) and orosomucoid 1-like 3 (ORMDL3) in airway remodeling among asthmatic mice and to observe the effects of budesonide (BUD) on their expression. Methods Thirty BALB/c mice were randomly divided into control, asthma, and BUD intervention group. The mice were sensitized and challenged with ovalbumin (OVA) to establish a mouse model of asthma. The BUD intervention group received aerosol inhalation of BUD dissolved in normal saline 30 minutes before each OVA challenge, while normal saline was used instead of OVA solution in the control group. The pathological changes in the airway were observed by hematoxylin-eosin staining and Masson staining. The interleukin-13 (IL-13) level in lung homogenate was measured by enzyme-linked immunosorbent assay. The mRNA expression of STAT6 and ORMDL3 was measured by RT-PCR. Results The asthma group showed more pathological changes in the airway than the control and BUD intervention groups, and the BUD intervention group had reduced pathological changes in the airway compared with the asthma group. The asthma and BUD intervention groups had significantly higher IL-13 levels and mRNA expression of STAT6 and ORMDL3 than the control group (P<0.05), and these indices were significantly higher in the asthma group than in the BUD intervention group (P<0.05). The Pearson correlation analysis showed that STAT6 mRNA expression was positively correlated with ORMDL3 mRNA expression (r=0.676, P=0.032). Conclusions STAT6 and ORMDL3 may be involved in the airway remodeling of mice, and BUD can reduce airway remodeling in asthmatic mice, possibly by down-regulating mRNA expression of STAT6 and ORMDL3.