减毒活菌卡介苗通过STAT6对哮喘小鼠肺组织Th1和Th2型细胞因子的影响

Bacille Calmette Guerin affects cytokines of Th1 and Th2 by signal transducer and activator of transcription 6 in lung of asthmatic mouse

目的:研究减毒活菌卡介苗(BCG)干预对哮喘小鼠呼吸道炎症、气管肺泡盥洗液(BALF)中细胞因子及肺组织信号转导和转录激活因子-6(STAT6)蛋白表达的影响。方法:将昆明小鼠30只随机分为正常对照组、哮喘组、BCG治疗组3组,每组小鼠都为10只。正常对照组以生理盐水致敏激发,以卵清白蛋白(OVA)致敏激发建立小鼠哮喘模型,BCG治疗组于OVA致敏前及后5天分别以BCG皮内注射干预,所有小鼠在最后一次抗原激发后24小时收集BALF,计数BALF中的白细胞总数及嗜酸性粒细胞(EOS)数目,苏木素-伊红(HE)染色观察小鼠肺组织病理形态学改变,用酶联免疫吸附试验(ELISA)检测BALF中IL-4、IFNγ-水平,以免疫组织化学法观察各组小鼠肺组织STAT6表达。结果:小鼠肺组织HE切片显示哮喘组有大量炎症细胞浸润。哮喘组、BCG治疗组小鼠肺组织STAT6蛋白表达和BALF中的白细胞总数、EOS计数、IL-4水平均较正常对照组升高(P<0.05);而与哮喘组比较,BCG治疗组肺组织STAT6蛋白表达和BALF中的白细胞总数、EOS计数、IL-4水平均降低(P<0.05)。与正常对照组比较,哮喘组BALF中的IFNγ-水平显著下降(P<0.01),而BCG治疗组BALF中的IFNγ-水平增加(P<0.05)。结论:BCG能抑制哮喘小鼠气道炎症、减少哮喘小鼠Th2型细胞因子IL-4的生成、提高Th1细胞因子IFNγ-的水平,其干预机制可能与BCG抑制哮喘小鼠肺组织STAT6蛋白的表达有关。

Objective：To evaluate the influence of Bacille Calmette Guerin（BCG）treament on the airway inflammation,the cytokines in bronchoalveolar lavage fluid and expression of signal transducer and activator of transcription 6（STAT6）in lung of asthmatic mouse.Methods：30 Kunming mice were randomly divided into control group,asthma group and BCG treatment group.The mice were sensitized and challenged with ovalbumin（OVA） to establish asthmatic model.The mice in BCG treatment group were injected intradermally with BCG 5 days before and after antigen sensitization.After the final OVA inhalation,to assemble the BALF and of mice at 24 h.To count the number of total cells and eosinophils in BALF.HE stained to observe lung inflammation.The concentration of cytokine interleukin 4（IL-4） and interferon γ（IFN-γ）in BALF were detected by enzyme linked immunosorbent assay（ELISA）.The expressions of STAT6 in lungs were detected by immunohistochemistry.Results：HE stained showed that the asthma group were infiltrated by generous inflammatory cell.The number of total cells,EOS,IL-4 in BALF and STAT6 in lung in asthma group were higher than those in control group（P0.05）.The number of total cells,EOS,IL-4 in BALF and STAT6 in lung in BCG treament group were higher than those in control group（P0.05）.The number of total cells,EOS,IL-4 in BALF and STAT6 in lung BCG treament group were lower than those in asthma group（P0.05）.Compared with control group,the level of IFN-γ was significantly decreased in asthma group（P0.01）,however,the level of IFN-γ was significantly higher in BCG treatment group（P0.01）.Conclusion：BCG can inhibit the airway inflammation of asthmatic mouse,decrease the production of Th2 cytokines like IL-4 and elevate Th2 cytokines such as IFN-γ,those may owing to BCG inhibit the expression of STAT6 in lung of asthmatic mouse.