应用白细胞介素12阻断GATA-3表达治疗小鼠支气管哮喘

Interleukin-12 blocking GATA-3 expression in treatment of bronchial asthma:an experimental study

目的观察T细胞特异转录因子GATA-3在支气管哮喘(哮喘)小鼠肺部的表达,探讨应用白细胞介素12(IL-12)阻 断GATA-3表达治疗支气管哮喘的可能性。方法:30只C57BL/6小鼠随机均分为正常对照组(A组)、哮喘组(B组)、IL-12 治疗组(C组)。B组和C组建立哮喘模型,于第1、3、7、9、25、26、27、28天,分别1次腹腔注射生理盐水(0.1ml)和IL-12(1 μg)。第31天收取各组6只小鼠的支气管肺泡灌洗液(BALF)测细胞成分,各组剩余小鼠H-E染色切片观察小鼠气管、肺组织 病理变化,免疫组化测定肺组织中GATA-3表达。结果:对照组无症状,哮喘组哮喘症状重,治疗组哮喘症状轻。在BALF中 嗜酸粒细胞百分比对照组为0,哮喘组为(20.0±4.0)%,治疗组为(0.2±0.1)%。在同一视野对照组支气管黏膜下未见炎性 细胞,哮喘组可见大量炎性细胞浸润,治疗组炎性细胞较哮喘组明显减少。免疫组化染色对照组无GATA-3表达,哮喘组GA- TA-3表达强,治疗组GATA-3无表达。结论:哮喘小鼠肺部存在GATA-3高表达,IL-12对小鼠支气管哮喘气道和肺部炎症 浸润有抑制作用,其机制可能与IL-12阻断哮喘GATA-3的表达有关。

Objective:To observe the expression of GATA-3in asthmatic mice lungs and to explore the feasibility of in-terleukin(IL-12)blockading GATA-3expression in treatment of bronchial asthma.Methods:C57BL/6mice were randomly divided into3groups:control group(group A),asthmatic model group(group B)and IL-12injection group(group C).Asth-matic models were established in group B and C.Normal saline(0.1ml)and IL-12(1μg)were injected in group B and C re-spectively on the1,3,7,9,25,26,27and28d.Six mice from each group were obtained for analyses of bronchoalveolar lavage fluid(BALF)on d31.The airway pathology changes and the expression of GATA-3were observed by hematoxylin/eosin(H-E)and immunohistochemistry respectively.Results:There was no symptom in group A,and the symptoms of group B were more severe than those of group C.Eosinophil(EOS)was not seen in the BALF of group A,while EOS in group B and group C were(20.0±4.0)%and(0.2±0.1)%respectively.In the same microscopic visual field,there was no inflam-mation cell in group A and a large number of inflammation cells in group B,but inflammation cells in group C were signifi-cantly decreased.Immunohistochemistry showed that the expression of GATA-3in group B was strong and no GATA expres-sion was found in group A and group C.Conclusion:The expression of GATA-3in asthmatic mice is high;IL-12can inhibit asthmatic airway and lungs inflammtion,whose mechanism may be the blockade of GATA-3expression in asthmatic models.[