布地奈德上调支气管哮喘小鼠肺组织IDO、抑制气道炎症和气道高反应性的研究  

Inhibition of airway inflammation and hyperresponsiveness by budesonide via upregulation of indoleamine 2, 3 dioxygenase in a routine model of acute asthma

作　　者：汪凤凤[1] 苗伟伟[1] 刘洪泱[1] 黄茂[1] 殷凯生[1] 周林福[1] 

机构地区：[1]南京医科大学第一附属医院呼吸内科,210029

出　　处：《国际呼吸杂志》2013年第9期652-656,共5页International Journal of Respiration

基　　金：国家自然科学基金（81170018）;江苏省医学重点人才项目（RC2011066）;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）;江苏省高校优势学科建设工程（JX10231801）;江苏省卫生国际交流支撑计划（201235）

摘　　要：目的研究布地奈德对急性支气管哮喘（简称哮喘）模型小鼠肺组织吲哚胺-2，3双加氧酶（IDO）表达、气道炎症和气道高反应性的干预作用。方法18只SPF级BALB／c小鼠随机分为正常组、哮喘组、布地奈德组。卵白蛋白（OVA）致敏和激发建立哮喘模型。末次激发24h后，测定气道对乙酰胆碱的反应性，HE染色观察气道炎症细胞浸润，ELISA法检测血清总IgE、OVA特异性IgE（OVA—sIgE）以及支气管肺泡灌洗液（BALF）Th2细胞因子（IL-4和IL-13）。Westernblot检测肺组织IDO蛋白表达。结果正常组小鼠气道阻力随乙酰胆碱浓度增加仅轻度增加，哮喘组气道阻力较正常组显著增高，布地奈德组气道阻力较哮喘组显著下降（P〈0．05）；哮喘组血清总IgE和OVA-sIgE、BALF炎症细胞总数和嗜酸粒细胞分类计数、Th2细胞因子水平较正常组显著增高，布地奈德组炎症指标较哮喘组显著降低（P〈0．05）；哮喘组肺组织IDO较正常组显著下降，布地奈德组肺组织IDO较哮喘组显著增高（P〈O．05）。结论布地奈德抑制急性哮喘模型气道炎症和气道高反应性，可能与上调肺组织IDO有关。Objective To investigate the inhibitory effects of aerosol, budesonide on the expression of indoleamine 2, 3 dioxygenase （IDO）, airway inflammation, and airway hyperresponsiveness in a murine model of bronchial asthma （asthma）. Methods 18 BALB/c mice were randomly divided into 3 groups, including the control group, ovalbumin （OVA） group and budesonide group. Mice were sensitized and challenged By OVA. 24 h after the last challenge, airway responsiveness to acetylcholine chloride （Ach） was measured. Hematoxylin eosin staining was used to assess the inflammatory cell infiltrates. Levels of Th2 cytokines （IL-4 and IL-13） in bronchoalveolar lavage fluid （BALF）, and total IgE and OVA-specific IgE （OVA-sIgE） in serum were relevantly detected by ELISA. The protein expression of IDO was determined by western blot analysis. Results The airway resistance in the OVA group was obviously increased in a dose-dependent manner following administration of Ach, whereas only a slight increase could be detected in the control group. Treatment with budesonide led to a sharp decrease in airway resistance compared with the OVA group （ P 〈0.05）. Total IgE and OVA-slgE in serum, total inflammatory ceils and differential eosinophils as well as Th2 cytokines in BALF were significantly increased in the OVA group. These inflammatory indices were remarkably decreased by treatment with budesonide （ P 〈0.05）. The pulmonary expression of IDO was apparently declined in the OVA group. Treatment with budesonide enhanced the pulmonary expression of IDO in comparison with the OVA group （ P 〈 0.05 ）. Conclusions Budesonide could inhibit the airway inflammation and hyperresponsiveness by upregulating the expression of IDO in allergic asthma.

关 键 词：支气管哮喘 吲哚胺2 3双加氧酶 布地奈德 树突状细胞 调节性T细胞 

分 类 号：R562.25[医药卫生—呼吸系统]