糖皮质激素对哮喘大鼠T-bet及γ-干扰素表达的影响  

Effects of Glucocorticoids on the Expression of T-bet and Interferone-γ in Asthma Model of Rats

作　　者：刘红兵[1] 陶晓南[1] 冯罡[1] 熊亮[1] 

机构地区：[1]华中科技大学同济医学院附属协和医院呼吸内科,卫生部呼吸疾病重点实验室,武汉430022

出　　处：《华中科技大学学报（医学版）》2008年第4期465-468,共4页Acta Medicinae Universitatis Scientiae et Technologiae Huazhong

摘　　要：目的研究糖皮质激素对哮喘大鼠肺组织T-bet及Th1类细胞因子γ-干扰素(IFN-γ)表达的影响,初步探讨糖皮质激素治疗哮喘的机制。方法用卵清蛋白建立哮喘模型,24只SPF级SD雄性大鼠随机分为3组:正常对照组、哮喘模型组、地塞米松组。留取支气管肺泡灌洗液(BALF)进行细胞计数及分类;采取双抗体夹心酶联免疫吸附试验测定BALF中IFN-γ的含量;应用免疫组化及流式细胞术测定肺组织中T-bet的表达。结果①哮喘组BALF中嗜酸性粒细胞占细胞总数百分比(EOS%)高于正常对照组及地塞米松组(P<0.01);②哮喘组BALF中IFN-γ水平低于正常对照组(P<0.01),地塞米松组BALF中IFN-γ水平则低于哮喘组(P<0.01);③免疫组化及流式细胞术显示,哮喘组与正常对照组相比,T-bet表达降低(P<0.01),地塞米松组T-bet表达则低于哮喘组(P<0.01)。结论IFN-γ、T-bet的低表达参与哮喘的病理生理过程;地塞米松使哮喘大鼠IFN-γ及T-bet表达下调的同时对Th2类细胞因子更加强烈的抑制,从而使Th1/Th2比例趋向平衡,可能为其抑制哮喘呼吸道炎症的重要作用机制之一。Objective To study the effects of glucocorticoid on the expression of T-bet and interferone （IFN）-γ in asthma model of rats in order to investigate the mechanism of glucocorticoid in the treatment of asthma.Methods Twenty-four male SD rats were randomly divided into control group, asthma group and dexamethasone-treated group. The asthma rat model was established by the ovalbumin （OVA） challenge methods. The cells in bronchoalveolar lavage fluid （BALF） were counted and classified. The concentrations of IFN-γ in BALF were measured by sandwich enzyme-linked immunosorbent assay. The expression of T-bet protein in lung tissue was detected by immunohistochemistry and flow cytometry. Results ①The ratio of eosinophils to the total cell number （EOS%） in asthma group was significantly higher than in control group and dexamethasone-treated group （P〈0.01）, ②The concertration of IFN-γ in BALF of asthma group was significantly lower than in control group, and the concentration of IFN-γ in dexamethasone-treated group was significantly lower than in asthma group （P〈0.01）, ③Immunohistochemistry and flow cytometry revealed that the expression level of T-bet protein in lung tissue of asthma group was significantly lower than in control group （P〈0.01）, and that in dexamethasone-treated group was significantly lower than in asthma group （P〈0.01）. The results from flow cytometry indicated that the percentage of T-bet positive cells in lung tissue in asthma group was lower than that in control group （P〈0.01） and that in dexamethasone-treated group was significantly lower than in asthma group （P〈0.01）. Conclusion The low expression of IFN-γ and T-bet in asthma rats is involved in the pathophysiological process of asthma development. Dexamethasone can down-regulate the expression of T-bet and IFN-γ and inhibit the Th2 cytokines, which may be one of the important mechanisms of dexamethasone suppressing the airway inflammation in asthma.

关 键 词：哮喘 Γ干扰素 T-BET 炎症 地塞米松 

分 类 号：R392.5[医药卫生—免疫学]