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 2,3dioxygenase in a murine 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：《中华哮喘杂志（电子版）》2013年第4期5-8,共4页Chinese Journal of Asthma(Electronic Version)

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)。Western blot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<0.05)。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 2,3dioxygenase(IDO),airway inflammation,and airway hyperresponsiveness in a murine model of bronchial asthma(asthma).Methods 18BALB /c mice were randomly divided into 3groups,including the control group,ovalbumin(OVA) group and budesonide group.Mice were sensitized and challenged by OVA.24hafter the last challenge,airway responsiveness to acetylcholine chloride(Ach) was measured.Hematoxylin &eosin staining was used to assess the inflammatory cell infiltrates.Levels of Th2cytokines(IL-4and IL-13) in bronchoalveolar lavage fluid(BALF),and total IgE and OVAspecific 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-sIgE in serum,total inflammatory cells and differential eosinophils as well as Th2cytokines 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]