布地奈德对呼吸道合胞病毒感染的哮喘小鼠肺损伤保护作用

摘要

Objective To explore the protective effect of budesonide on lung injury induced by respiratory syncytial virus (RSV) in asthmatic mice.Methods Thirty-six male BALB/c mice aged 6-8 weeks were randomly divided into control group,model group,and budesonide group(n =12 in each group).The mice in model group and budesonide group were intraperitoneally injected with OVA for sensitization and atomization inhalation to establish the model of asthma.The mice in control group were given normal saline.At day 28,30,32,RSV virus was given intranasally every other day to establish an acute viral infection model.The mice in control group were treated with saline.The mice in budesonide group were given budesonide inhalation for 30 min once a day at day 27-33,and the bronchoalveolar lavage fluid(BALF) was collected to count the white blood cells in BALF at day 34.The pathological changes of lung tissues were observed by HE.The expression of HMGB1 and TLR4 in lung tissue was observed by immunohistochemical method.The expression of cytokine IFN-γ,IL-2,IL-13 and eosinophil chemokines in BALF and serum was detected by ELISA.Results Compared with control group,the number of eosinophils,neutrophils and macrophages in the BALF increased in model group and budesonide group(P ＜ 0.01).Compared with model group,the total number of leukocytes in BALF was significantly decreased in budesonide group(P ＜ 0.01),the levels of cytokines,eosinophil chemokines and IL-13 in BALF and serum were decreased (P ＜ 0.01),while IFN-γand IL-2 levels were significantly increased(P ＜ 0.01).Pathological results of lung tissue showed that the inflammatory cell infiltration decreased in budesonide group and the expression of HMGB1 and TLR4 in lung tissue was inhibited.Conclusion Budesonide can reduce the airway inflammation in children with RSV infection and inhaled budesonide has a certain therapeutic effect in RSV-infected asthmatic mice.%目的 观察布地奈德对呼吸道合胞病毒(RSV)感染的哮喘小鼠模型肺部损伤的保护作用. 方法 6-8周龄雄性BALB/c小鼠36只,随机分为对照组、模型组、布地奈德组,每组12只.模型组和布地奈德组用卵清蛋白腹腔注射致敏和雾化吸入激发,建立小鼠哮喘模型,对照组用生理盐水替代.于28,30,32 d,用RSV病毒液隔日滴鼻,连续3次,建立急性病毒感染哮喘模型.对照组用生理盐水滴鼻.布地奈德组于27-33 d给予布地奈德雾化吸入,每日1次,每次30 min,第34天给予各组小鼠肺泡灌洗,收集支气管肺泡灌洗液(BALF),计数BALF中的白细胞数目;制作肺组织的病理切片,HE染色光镜观察肺组织病理变化;免疫组化法观察HMGB1、TLR4在肺组织中的表达;ELISA检测BALF与血清中细胞因子IFN-γ、IL-2、IL-13及嗜酸性粒细胞趋化因子. 结果 与对照组相比,模型组与布地奈德组小鼠BALF中嗜酸性粒细胞、中性粒细胞及巨噬细胞升高(P＜0.01).与模型组相比,布地奈德组小鼠BALF中白细胞总数明显降低(P＜0.01),BALF及血清中细胞因子,嗜酸性粒细胞趋化因子、IL-13水平降低(P＜0.01);IFN-γ、IL-2水平明显增高(P＜0.01).肺组织病理结果显示吸入布地奈德可减少小鼠肺组织炎症细胞浸润,抑制HMGB1、TLR4在肺组织中的表达. 结论 布地奈德可减轻RSV感染的哮喘小鼠气道炎症,吸入布地奈德对于RSV感染的哮喘小鼠具有一定的治疗作用.