过表达XB130抑制哮喘小鼠气道高反应性和气道炎症

摘要

Objective:To investigate the effect of XB 130 on the airway inflammation and hyperresponsiveness in a murine asthmaric model.Methods:C57 mice were randomly divided into 4 groups with 9 mice each:control group (CON),Asthma group (AS),Adenovirus contral group (Ad-vector+AS) and XB130 overexpression group (Ad-XB130+AS).A murine asthmaric model was induced by ovalbumin (OVA) administration.Ad-vector and Ad-XB130 were injected intravenously.After the last antigen challenge for 24 h,the bronchi alveolar lavage fluids (BALF)have been collected.Airway hyperresponsiveness to methacholine (Mch) was measured.The expression of XB 130 in lung tissues was evaluated using RT-PCR and Western blotting respectively.The content of OVA-specific IgE in serum was detected using ELISA.The cell counts of eosinophile granulocyte (EOS) were calculated.The secretion ofIL-4,IL-5,IL-13 and IFN-γ were determined using ELISA.Results:XB130 was reduced in the lung tissue of asthma mice.The mRNA and protein expression of XB130 were increased in Ad-XB130 asthmatic mice.Overexpression XB130 reduced the airway hyperresponsiveness induced by methacholine (Mch).The number of EOS in Ad-XB130+AS group (17± 4) was decreased compared with Ad-vector+AS group (48± 3).Moreover,forcing expression of XB 130 (0.051 ± 0.002) reduced the content of OVA-specific IgE compared with vector control group (0.128± 0.007).In addition,XB130 inhibited the secretion of IL-4,IL-5 and IL-13,promoted the production of IFN-γ in BALF and lung tissues.Conclusion:Overexpression of XB130 inhibited the airway inflammation and hyperresponsiveness in asthrnatic mice.%目的:研究XB130在哮喘小鼠气道高反应(airway hyperresponsiveness,AHR)和气道炎症中的作用.方法:36只C57小鼠分为4组:正常对照组(Control,CON)、哮喘组(Asthma,AS)、腺病毒载体组(Ad-vector+AS)和腺病毒过表达XB130组(Ad-XB 130+AS).采用卵白蛋白(ovalbumin,OVA)建立小鼠过敏性哮喘模型,后两组小鼠分别尾静脉注射Ad-vector和Ad-XB130.最后一次雾化吸入后24小时进行气道高反应试验,收集支气管灌洗液(bronchi alveolar lavage fluids,BALF).采用RT-PCR和Western blotting方法检测XB130表达.ELISA法检测血清中OVA特异性IgE的含量.直接计数法计算BALF中嗜酸性粒细胞(eosinophile granulocyte,EOS)数量.ELISA方法用于检测BALF和肺组织中IL-4、IL-5、IL-13和IFN-γ 的分泌.结果:哮喘小鼠肺组织中XB130表达减少,过表达XB130其mRNA和蛋白表达水平显著升高.过表达XB130降低醋甲胆碱(methacholine,Mch)诱导的气道高反应.与载体对照组(48±3)相比,XB130过表达(17± 4)EOS数量显著减少.同时,过表达XB130(0.051± 0.002)较载体对照组(0.128± 0.007)IgE含量减少.此外,XB130抑制哮喘小鼠中IL-4、IL-5和IL-13并促进IFN-γ分泌.结论:过表达XB130可抑制哮喘模型小鼠气道高反应性和炎症反应.