转录因子T-bet/GATA-3在支气管哮喘小鼠中的表达及地塞米松的干预作用
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南京市卫生局基金资助项目(YKK0435)


Inhibitory effects of dexamethasone on expression of transcription factor GATA-3 and T-bet in ashmatic mice
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    目的:探讨核因子T-bet/GATA-3在支气管哮喘小鼠发病机制中的作用,观察地塞米松干预后T-bet-GATA-3 mRNA的变化-方法:建立卵清蛋白(OVA)诱导的哮喘小鼠模型;24只BALB/c小鼠随机分为正常组-哮喘组及地塞米松治疗组,地塞米松腹腔注射(2 mg/kg)给药-HE染色观察气道炎症变化;采用RT-PCR方法检测T-bet-GATA-3 mRNA的表达;流式细胞技术检测小鼠脾脏CD4+T细胞IFN-γ-IL-4水平-结果:与正常组相比,哮喘组小鼠GATA-3 mRNA表达显著增加(P < 0.05),T-bet mRNA水平明显降低(P < 0.05),IFN-γ水平明显降低(P < 0.01),IL-4水平明显升高(P < 0.05);经地塞米松干预后,肺组织GATA-3-T-bet mRNA均有所降低,以GATA-3 mRNA降低更为明显,IL-4表达明显降低(P < 0.05),而IFN-γ水平有减少倾向-结论:支气管哮喘小鼠T-bet/GATA-3表达失衡与气道炎症密切相关,地塞米松通过抑制GATA-3和T-bet 的表达,调节IL-4/IFN-γ比率并纠正Th1/Th2平衡失调,可能是其治疗哮喘的机制之一-

    Abstract:

    Objective:To indentify the expression of transcription factor GATA-3 and T-bet in asthmatic mice and observe the change of T-bet/GATA-3 balance interfered by dexamethasone. Methods:The BLAB/C mice asthma model was induced by classic method with ovalbumin; Twenty-four male mice were randomly divided into a control group, an asthmatic group and a dexamthasone(DEX)-treated asthmatic group in which mice were injected with dexamthasone(2 mg/kg) intraperitoneally. The pathological changes of lung were measured by HE staining, the expression of GATA-3 and T-bet mRNA of lung were measured by RT-PCR. The levels of IL-4 and IFN-γ in mice spleen CD4+T cell were measured by flow cytometry. Results:In the asthmatic group, the expression of GATA-3 mRNA and the level of IL-4 were significantly elevated compared to those in the control group(P < 0.05), the expression of T-bet mRNA and the level of IFN-γ were decreased compared to those in the control group(P < 0.05;P < 0.01). Both of GATA-3 and T-bet mRNA decreased after DEX treatment, and the decreasing degree of GATA-3 was more than that of T-bet. The expression of IL-4 and IFN-γ were depressed simultaneously and the downregulation of IL-4 was more than that of IFN-γ after DEX treatment. Conclusion:The imbalance of transcription factor GATA-3 and T-bet had a closely correlation with the airway inflammation in asthmatic mice. DEX could reverse the ration of IL-4/IFN-γ and regulate the balance of Th1 and Th2 through inhibiting both GATA-3 and T-bet.

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俞海国,钱丽娟,钱小青,李 娟,张雅媛,郭翼红.转录因子T-bet/GATA-3在支气管哮喘小鼠中的表达及地塞米松的干预作用[J].南京医科大学学报(自然科学版),2009,29(1):55-59

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  • 收稿日期:2008-07-04
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