雾化吸入干扰素γ阻断GATA-3表达防治哮喘的实验研究

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

目的研究雾化吸入IFNγ对支气管哮喘(哮喘)防治作用及其机制。方法以Balbc小鼠采用卵蛋白(OVA)、氢氧化铝建立哮喘模型(C组),于23d至30d雾化吸入IFNγ12μg1次d,31d时取肺泡灌洗液(BALF)测定细胞成分,白细胞介素4(IL4)、白细胞介素5(IL5)浓度,取血测定血浆IgE水平,观察肺组织病理学变化及GATA3的表达。设正常对照组(A组)和哮喘模型PBS处理组(B组)。每组小鼠12只。结果①C组BALF中的嗜酸性粒细胞(EOS)数量明显低于B组(P<0.01);②C组BALF中的IL4和IL5的水平明显低于B组(P<0.01);③C组血浆中总IgE和OVA特异性IgE水平显著低于B组(P<0.01);④B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为主的炎症细胞浸润,而C组小鼠的上述炎症性改变则明显减轻;⑤免疫组化显示B组肺组织中GATA3的表达明显增加,而C组GATA3的表达明显减少。结论雾化吸入IFNγ可抑制哮喘鼠IL4、IL5的合成,抑制气道炎症,抑制EOS在气道内的炎性浸润及降低血浆总IgE和OVA特异性IgE水平,其机制可能与IFNγ阻断GATA3的表达,从而继发抑制Th2型反应有关。

Objective To investigate the role and the mechanism of IFN-γ on prevention and treatment of bronchial asthma. Methods Group C （ 12 Balb/c mice） was the asthmatic model established by using ovalbumin （OVA） absorbed to aluminum hydroxide. IFN-γ of 12μg were nebulized and given to the mice in group C on day 23 to 30 once daily. The cellular composition of bronchoalveolar lavage fluid （BALF） was collected and analyzed on day 31. The levels of IL-4, IL-5, and IgE in serum were determined; the change of pathology and the GATA-3 expression were observed. There are control group （group A） and asthmatic model group （treated with PBS, group B） in the experiment with 12 mice in each group. Results ① Eosinophils in BALF of group C was much notably decreased than that of group B （ P 〈 0.01 ）. ② The levels of IL-4 and IL-5 in BALF of group C were much significantly decreased than that of group B （ P 〈 0.01 ）. ③ The levels of total IgE and ovalbumin-specific IgE in serum of group C were much significantly decreased than that of group B （ P 〈 0.01 ）. ④ Bronchi smooth muscle hypertrophing, mucous hyperemia, mucous layer thickening, and inflammatory cell infiltration were appeared in group B. Phlegmasia was appeared in the bronchi of group B, which was filled with lots of mucus. In contrast, the inflammatory reaction in group C was much less. ⑤ Expression of GATA-3 was obviously increased in group B while expression of GATA-3 decreased bitabkt in group C. IFN-γ could inhibit the levels of IL-4, IL5, asthntic airway inflammation, eosinophils infiltration, total IgE, and evalburmin-specific IgE of the mice, whose mechanism may be explained by that IFN-γ could restrain the Th2 reaction by blockade GATA-3 expression in the lung tissue.