地塞米松对呼吸道合胞病毒感染哮喘加重小鼠气道TSLP分泌及炎症的影响

Effect of dexamethasone upon secretion of thymic stromal lymphopoietin and airway inflammation in respiratory syncytial virus-induced asthma exacerbation of mice

目的:探讨地塞米松(DEX)对呼吸道合胞病毒(RSV)感染哮喘加重小鼠胸腺基质淋巴细胞生成素(TSLP)分泌及气道炎症的影响。方法:雌性BALB/c小鼠32只,随机分成4组,分别为磷酸盐缓冲液(PBS)对照组、鸡卵白蛋白(OVA)组、OVA/RSV组、OVA/RSV/DEX组;应用OVA腹腔注射致敏、OVA气道雾化结合RSV滴鼻激发哮喘,地塞米松1mg/kg肌肉注射;无创肺功能检测各组小鼠气道反应性;ELISA法检测小鼠血清IL-4、IL-5、IL-13、IFNγ-和气管灌洗液(BALF)TSLP含量;小鼠肺组织病理观察炎症反应,免疫组化观察小鼠气道上皮细胞TSLP表达水平。结果:无创肺功能检测显示地塞米松抑制RSV感染哮喘加重小鼠气道反应性的增高,OVA/RSV/DEX组小鼠Penh值明显低于OVA/RSV组(P<0.01);OVA/RSV/DEX组小鼠血清IL-4、IL-5、IL-13、IFNγ-浓度[分别为(86.78±27.04)、(227.66±40.87)、(194.65±73.27)和(17.33±3.06)pg/ml]和BALF中TSLP浓度[(1 873±10)pg/ml],均明显低于OVA/RSV组[分别为(274.2±103.7)、(293.3±46.1)、(330±93.5)、(30.1±5.7)、(2 127±46)pg/ml](P<0.01);病理观察显示地塞米松显著减轻RSV感染哮喘小鼠气道炎症细胞浸润;免疫组化染色证实地塞米松抑制RSV感染哮喘小鼠气道上皮细胞TSLP表达。结论:地塞米松可以抑制RSV感染哮喘加重小鼠气道上皮细胞表达TSLP,减轻RSV感染哮喘加重小鼠气道炎症反应。

Objective：To investigate the effects of dexamethasone（DEX） on the production of thymic stromal lymphopoietin（TSLP） and airway inflammation of respiratory syncytial virus-induced asthma exacerbation in mice.Methods：32 female BALB/c mice were randomly divided into four groups：PBS control group,OVA group,and OVA/RSV group,and OVA/RSV /DEX group.Mice were sensitized by OVA and stimulated with nebulized OVA.RSV was inoculated into murine nasal cavity and 1 mg/kg of DEX was intramuscularly administered.BUXCO noninvasive murine lung function detection instrument was used to examine the airway response to metacholine.ELISA was used to detect IL-4,IL-5,IL-13 and IFN-γ in murine serum and TSLP in supernatants of bronchoalveolar lavage fluid（BALF）.Murine lung specimens were stained with HE to observe inflammation and immunohistochemical technique was employed to observe the production of TSLP in murine airway epithelial cells.Results：The animal experiment demonstrated that the murine airway responsiveness to metacholine in RSV/OVA/DEX group was lower than that in OVA/RSV group（P〈0.01）.The levels of IL-4[（86.78±27.04） pg/ml],IL-5[（227.66±40.87） pg/ml],IL13[（194.65±73.27） pg/ml],IFN-γ[（17.33±3.06） pg/ml]in murine serum and TSLP[（1 873±10） pg/ml] in BALF of RSV/OVA/DEX group were significantly lower than those in OVA/RSV group[（274.2±103.7）,（293.3±46.1）,（330±93.5）,（30.1±5.7） pg/ml and（2 127±46） pg/ml respectively,all P〈0.01].Less infiltration of airway inflammatory cells in OVA/RSV/DEX group was observed than that in OVA/RSV group.Immunohistochemical staining of TSLP also showed a lower production of TSLP in airway epithelial cells of OVA/RSV/DEX group than in OVA/RSV group.Conclusion：Dexamethasone can inhibit the elevated production of TSLP in airway epithelial cells after RSV infection and relieve airway inflammation of RSV-induced asthma exacerbation in mice.