BALB/c小鼠哮喘进展过程中T-bet和GATA3的表达变化

The changes of T-bet and GATA3 during development of asthma in BALB/c mice

目的:初步探讨转录因子T-bet和GATA3在小鼠哮喘模型哮喘进展过程中的改变及其意义。方法:18只BALB/c小鼠随机分为正常对照组、哮喘组和药物组(地塞米松组),每组各6只。采用Western blot法检测各组小鼠肺组织T-bet和GATA3的表达,同时运用流式细胞仪检测小鼠脾细胞胞内细胞因子白介素4(IL-4)和干扰素γ(IFN-γ)的表达。结果:哮喘组与正常对照组相比,药物组与哮喘组相比,肺组织T-bet和GATA3均有明显改变(P<0.01)。哮喘组T-bet明显减低,而GATA3明显升高;地塞米松治疗后,T-bet和GATA3均明显减低,后者减低更为明显。流式细胞仪分析显示:哮喘组CD4+T细胞细胞内IL-4/IFN-γ的比值显著高于对照组(P<0.01);经地塞米松处理后的哮喘小鼠CD4+T细胞细胞内IL-4/IFN-γ的比值显著降低(P<0.01)。结论:转录因子T-bet和GATA3与哮喘进展密切相关,调控它们的表达,可以改变IL-4/IFN-γ比值,纠正哮喘的Th2漂移,可能成为哮喘治疗的新靶点。

Objective:To study the changes of transcription factor T-bet and GATA3 and their significance during development of asthma in BALB/c mice.Methods:Eighteen BALB/c mice were divided into 3 groups randomly:control group,asthma group,and dexamethasone(DXM) treated group, with 6 mice in each.Expression of T-bet and GATA3 in lung tissue was detected by Western blot and the intracellular cytokines interleukin 4 and interferon-γ in CD4+T cells were measured by flowcytometry.Results:By comparing asthma group vs control group and DXM treated group vs asthma group, the level of expression of T-bet in asthma group decreased significantly(P<0.01) and that of GATA3 increased significantly(P<0.01). After therapy by DXM, the levels of T-bet and GATA3 decreased significantly(P<0.01),with the decreased degree of GATA3 more than that of T-bet. The results of flowcytometry indicated that the ratio of intracellular cytokines IL-4/IFN-γ of CD4+T cell in asthma group was much higher than that of in control group(P<0.01), after therapy of DXM, the ratio of intracellular cytokines IL-4/IFN-γ decreased significantly(P<0.01).Conclusion:The transcription factor T-bet and GATA3 are associated with asthma ongoing closely. To reverse the ratio of IL-4/IFN-γ of CD4+T cell by regulating T-bet and GATA3 expression may improve the inflammatory reactions and could be a new way in treating asthma.