雾化吸入γ干扰素阻断GATA-3表达治疗支气管哮喘  

Treatment of bronchial asthma by blockade of GATA-3 expression with nebulized interferon gamma

作　　者：黄艳[1] 陈吉泉[1] 修清玉[1] 

机构地区：[1]第二军医大学附属长征医院呼吸内科,上海200003

出　　处：《上海医学》2006年第9期640-643,F0003,共5页Shanghai Medical Journal

基　　金：国家自然科学基金(30200116;30170406)

摘　　要：目的研究雾化吸入γ扰素(IFN-γ)对支气管哮喘的防治作用及机制。方法采用卵蛋白(OVA)、氢氧化铝建立BALB/c小鼠哮喘模型。IFN-γ雾化吸入组(C组)于模型建立第23天至第30天每日1次雾化吸入IFN-γ12μg,第31天取肺泡灌洗液(BALF)测定细胞成分、白介素(IL)-4、IL-5浓度,取血测定血浆IgE水平,观察肺组织病理学变化及转录因子GATA-3的表达。设正常对照组(A组)和哮喘模型磷酸盐缓冲液(PBS)处理组(B组)。每组12只小鼠。结果C组BALF中的嗜酸性粒细胞(EOS)为0．005±0．003,明显低于B-组的O．211 4-O．067(P<0．01)；C组BAI。F中的IL-4为(6．8±3．7)pg／mL,IL-5为(12．6±4．8)pg/mL,均明显低于B组的(90．5±22．4)pg/mL和(55．6±10．7)pg/mL(P＜0．01)；C组血浆中总IgE为(38．8±9．7)μg/mL,OVA特异性IgE为(19．2±4．8)U/mL,明显低于B组的(67．2±9．7)μg/mL和(34．6±7．8)U/mL(P＜0．01)；B组支气管平滑肌肥厚,黏膜充血、水肿．黏膜层增厚,并有EOS为主的炎性细胞浸润,管腔内可见黏液栓,支气管壁周围有EOS为主的炎性细胞浸润,而C组小鼠的上述炎症性改变明显减轻；免疫组织化学显示B组肺组织中GATA-3的表达明显增加。而C组GATA-3的表达明显减少。结论雾化吸入IFN-γ可以抑制哮喘鼠IL-4、IL-5的合成、抑制气道炎症、抑制EOS在气道内的炎性浸润及血浆中总IgE和OVA特异性IgE水平,其机制可能与IFN-γ阻断GATA-3的表达,从而继发抑制辅助性T细胞2型反应有关。Objective To investigate the efficacy and the mechanism of the action of nebulized interferon gamma （IFN-γ） in prevention and treatment of bronchial asthma. Methodes Ovalbumin （OVA） adsorbed to aluminum hydroxide was used to construct clinical bronchial asthma model in BALB/c mice （group C）, nebulized IFN-γ 12 μg was inhaled on day 23 to day 30 once daily. The bronchalveolar lavage fluid （BALF） was collected on day 31, of which the cellular constituents, levels of IL-4, IL-5 and IgE were determined, together with the pathologic changes and expression of GATA-3 were observed. The normal control group （group A） and the asthmatic model group （group B） consisted of 12 mice for each. Results Decrease of eosinophils （0. 005 ±0. 003） was seen in BALF of group C as comparing with group B （0.211±0.067, P〈0.01）, the levels of IL-4 [（6.8±3. 7） pg/mL] and IL-5 [（12.6±4.8）pg/mL] decreased significantly in comparing with group B nIL-4 （90. 5±22.4）pg/mL and IL-5 （55.6±10.7）pg/mL, P〈0.01]. The serum levels of total IgE [（38.8±9.7）μg/mL] and ovalbumin specific IgE [（19.2±4.8）U/mL] decreased significantly in comparing with those of group B [（67.2±9. 7）μg/mL] and [（34.6±7.8）U/mL, P〈0.01]. In group B, there were bronchial smooth muscle hypertrophy, mucosal congestion and edema thickening with inflammatory cells infiltration mainly of eosinophils, and abundant mucus thrombi inside the bronchial lumen. In group C, the above mentioned changes were much more ameliorated. Immunohistochemistry showed significant increase of GATA 3 expression in the lung tissue of group B but much lesser than that in group C. Conclusion IFN-γ can inhibit IL-4, IL-5 and the airway inflammation with eosinophilic infiltration and the serum levels of total IgE and ovalbumin-specific IgE, probably through the mechamism of restraining the Th2 reaction by blockade of GATA-3 expression in the lung tissue. （Shanghai Med J, 2006, 29=640-643）

关 键 词：Γ-干扰素 支气管哮喘 GATA-3 雾化吸入 

分 类 号：R562.25[医药卫生—呼吸系统]