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布地奈德抑制支气管哮喘小鼠TSLP及Th2优势免疫作用的研究
引用本文:王文璐,李红岩,苗伟伟,汪凤凤,刘洪泱,黄 茂,殷凯生,周林福.布地奈德抑制支气管哮喘小鼠TSLP及Th2优势免疫作用的研究[J].南京医科大学学报,2012(9):1207-1210.
作者姓名:王文璐  李红岩  苗伟伟  汪凤凤  刘洪泱  黄 茂  殷凯生  周林福
作者单位:南京医科大学第一附属医院呼吸内科,江苏 南京 210029;南京市市级机关医院呼吸科,江苏 南京 210018;南京医科大学第一附属医院呼吸内科,江苏 南京 210029;南京医科大学第一附属医院呼吸内科,江苏 南京 210029;南京医科大学第一附属医院呼吸内科,江苏 南京 210029;南京医科大学第一附属医院呼吸内科,江苏 南京 210029;南京医科大学第一附属医院呼吸内科,江苏 南京 210029;南京医科大学第一附属医院呼吸内科,江苏 南京 210029;南京医科大学第一附属医院呼吸内科,江苏 南京 210029
基金项目:国家自然科学基金(81170018,30570797,30400191);江苏省医学重点人才项目(RC2011066);人事部和教育部留学回国人员科技启动项目(200886,FD09);江苏省333高层次人才培养工程(201115);江苏省高校自然科学研究项目(11KJB320008);江苏省卫生国际交流支撑计划(201235)
摘    要:目的:研究布地奈德抑制哮喘小鼠Th2优势应答的作用及其机制?方法:选择24只6周龄SPF级BALB/c小鼠,随机分为3组:正常对照组?哮喘模型组?布地奈德组,每组8只?卵白蛋白(OVA)致敏和激发制作哮喘模型?小鼠末次雾化吸入激发24 h后,采用小鼠肺功能仪检测气道对乙酰胆碱(Ach)的阻力;苏木精-伊红(HE)染色观察气道炎症浸润情况;支气管肺泡灌洗液(BALF)瑞氏染色计数嗜酸性粒细胞百分比;酶联免疫吸附试验(ELISA)测定血清总IgE?BALF液中白细胞介素4(IL-4)和IL-13;免疫印迹(Western blot)测定肺组织胸腺基质淋巴细胞生成素(TSLP)表达水平?结果:与正常对照组比较,哮喘模型组气道阻力?气道炎症?血清总IgE?BALF中Th2细胞因子(IL-4?IL-13)以及肺组织TSLP蛋白表达明显增高(P < 0.05)?与哮喘模型组比较,布地奈德组各项观测指标均明显降低(P < 0.05)?结论:布地奈德通过降低肺组织TSLP表达?抑制Th2细胞因子水平而降低哮喘气道炎症和气道高反应性,可能是糖皮质激素治疗哮喘的重要机制?

关 键 词:支气管哮喘    布地奈德    胸腺基质淋巴细胞生成素    2型辅助性T细胞
收稿时间:2012/2/14 0:00:00

The inhibitory effect of budesonide on TSLP-induced Th2-dominated immune response in asthmatic mice
WANG Wen-lu,LI Hong-yan,MIAO Wei-wei,WANG Feng-feng,LIU Hong-yang,HUANG Mao,YIN Kai-sheng and ZHOU Lin-fu.The inhibitory effect of budesonide on TSLP-induced Th2-dominated immune response in asthmatic mice[J].Acta Universitatis Medicinalis Nanjing,2012(9):1207-1210.
Authors:WANG Wen-lu  LI Hong-yan  MIAO Wei-wei  WANG Feng-feng  LIU Hong-yang  HUANG Mao  YIN Kai-sheng and ZHOU Lin-fu
Institution:Department of Respiratory Medicine,the First Affiliated Hospital of NJMU,Nanjing 210029;Department of Respiratory Medicine,Nanjing Governmental Hospital,Nanjing 210018,China;Department of Respiratory Medicine,the First Affiliated Hospital of NJMU,Nanjing 210029;Department of Respiratory Medicine,the First Affiliated Hospital of NJMU,Nanjing 210029;Department of Respiratory Medicine,the First Affiliated Hospital of NJMU,Nanjing 210029;Department of Respiratory Medicine,the First Affiliated Hospital of NJMU,Nanjing 210029;Department of Respiratory Medicine,the First Affiliated Hospital of NJMU,Nanjing 210029;Department of Respiratory Medicine,the First Affiliated Hospital of NJMU,Nanjing 210029;Department of Respiratory Medicine,the First Affiliated Hospital of NJMU,Nanjing 210029
Abstract:Objective:To investigate the inhibitory effects and mechanism of budesonide on Th2-dominated immune response in a murine model of asthma. Methods:Twenty-four 6-week-old healthy BALB/c mice,SPF grade,were randomly divided into 3 groups,including the normal control group,the asthma group,and the budesonide group. Mice in the budesonide group were exposed to an aerosol of budesonide daily during ovalbumin(OVA) challenge. The murine asthma model was established by OVA sensitization and challenge. Twenty-four hours after the last airway provocation,acetylcholine (Ach) was administered via caudalis vein,and the airway resistance was measured by pulmonary function detector. The levels of IL-4 and IL-13 in branchoalveolar lavage fluid (BALF) and total IgE in serum were determined by enzyme-linked immunosorbent assay (ELISA). Total and differential cell counts in BALF were calculated by light microscopy. The airway inflammatory infiltration was detected by haematoxylin and eosin (HE) staining. The pulmonary thymic stromal lymphopoietin was determined by Western blot analysis. Results:As compared with the control group,the airway hyperreactivity,airway inflammation,cell count and eosinophil percentage in BALF,levels of total serum IgE and BALF IL-4 and IL-13,and thymic stromal lymphopoietin (TSLP) expression in the lung were significantly increased in the asthma group (P < 0.05). As compared with the asthma group,all the above indices mentioned in the budesonide group were decreased significantly(P < 0.05). Conclusion:Budesonide could reduce the allergen-induced airway inflammation and hyperreactivity by downregulating the expressions of pulmonary TSLP and Th2 cytokines,which may be an important mechanism of corticosteroids for the treatment of asthma.
Keywords:bronchial asthma  budesonide  thymic stromal lymphopoietin(TSLP)  T-helper type 2
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