TSLP-OX40信号通路对哮喘小鼠气道重塑的影响及地塞米松的干预作用

The role of TSLP-OX40 signal transduction pathway and the prevention effects of dexamethasone in the course of airway remodeling of asthmatic mice

目的探讨TSLP-OX40信号通路对哮喘小鼠气道炎症和气道重塑的影响及地塞米松的干预作用。方法 SPF级BALB/C雌性小鼠30只,随机分为对照组、哮喘组、地塞米松组,每组10只。采取卵清白蛋白(OVA)致敏和激发建立慢性哮喘小鼠模型;检测肺泡灌洗液中细胞分类计数;HE染色观察炎症细胞浸润;支气管壁厚度及平滑肌厚度测定;Western blot检测肺组织TSLP蛋白、OX40蛋白的表达。结果通过HE染色观察哮喘组气道炎症浸润明显;哮喘组小鼠支气管壁厚度及平滑肌厚度较对照组增加(P<0.05),地塞米松组支气管壁厚度与平滑肌厚度低于哮喘组(P<0.05)。哮喘组小鼠肺组织TSLP蛋白与OX40蛋白的表达高于对照组(P<0.05),地塞米松组TSLP蛋白与OX40蛋白表达较哮喘组下降(P<0.05)。结论 TSLPOX40信号通路的活化促进了哮喘小鼠气道重塑的发生,地塞米松可能通过抑制TSLP-OX40信号通路的活化从而治疗哮喘。

Objective To investigate the role of TSLP（thymic stromal lymphopoietin）-OX40 signal transduction on airway inflammation and airway remodeling and to study the effect of dexamethasone treatment in chronic athmatic mice. Methods Thirty BALB/c mice were randomly divided into three groups：a control group,an asthmatic group and a dexamethasone-treated group.The asthmatic mouse models were established by intraperitoneal injection and inhalation with ovalbumin（OVA）. The cells in the broncho-alveolar lavage fluid（BALF） were counted and classified. HE staining was used to observe airway inflammation and remodeling. The thickness of bronchial airway（Wam/Pbm） and the bronchial smooth musle thickness（Wat/Pbm） were measured. The protein expression of TSLP and OX40 were determind by western blotting. Results Compared with the control group and the dexamethasone-treated group,the inflammation of asthmatic group is most obviously by HE staining. Wam/Pbm and Wat/Pbm in athmatic group were higher than those of control group（P〈0.05）. The above index in dexamethasone-treated group were lower than athmatic group（P〈0.05）. The level of TSLP protein and OX40 protein in athmatic group were higher than those in control group（PO.05）,which were reduced by dexamethasone-treated group compared with the asthmatic group（P〈0.05）. Conclusion TSLP-OX40 signal transduction may play an important role in the course of airway remodeling in chronic athmatic mice,dexamethasone can treat asthma by inhibitting activation of the TSLP-OX40 signaling pathway.