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目的探讨转录因子GATA-3靶向寡核苷酸(ODN)“圈套”策略对哮喘小鼠气道炎症的治疗作用。方法 32只小鼠随机均分为四组:正常对照(A)组、哮喘模型(B)组、“圈套”ODN治疗(C)组和变异“圈套”(D)组。通过气道给药的方式,将GATA-3靶向ODN及突变的ODN转染至哮喘小鼠肺部,应用流式细胞术检测哮喘小鼠脾CD4+T细胞白细胞介素(IL)4、γ干扰素(IFN-γ)水平,ELISA法检测肺组织IL-5、IL-13表达,Western blot法检测肺组织GATA-3蛋白表达,HE染色评价肺组织病理变化。结果 B组小鼠肺组织GATA-3蛋白表达、IL-5和IL-13水平均较A组增加(P<0.01或P<0.05);与B组相比,C组IL-4、IL-5及IL-13水平减少,IFN-γ/IL-4比值增高(P<0.05),小鼠气道炎症明显减轻;而D组上述各指标与B组比较差异无统计学意义(P>0.05)。结论 GATA-3靶向ODN“圈套”通过特异性阻断GATA-3活性,有效地抑制Th2型细胞因子的产生,从而减轻哮喘小鼠气道炎症反应。
Objective To investigate the therapeutic effect of transcription factor GATA-3 targeting oligonucleotide (ODN) and “snare” strategy on airway inflammation in asthmatic mice. Methods Thirty - two mice were randomly divided into four groups: normal control group (A), asthma model group (B), “snare” ODN treatment group (C) and mutation “snare” group. The GATA-3 targeting ODN and mutant ODN were transfected into the lungs of asthmatic mice by airway administration. The levels of interleukin (IL) 4 in spleen CD4 + T cells of asthmatic mice were detected by flow cytometry, The expression of IL-5 and IL-13 in lung tissue were detected by ELISA. The expression of GATA-3 protein in lung tissue was detected by Western blot. The pathological changes of lung tissue were evaluated by HE staining. Results Compared with group B, the expression of GATA-3, IL-5 and IL-13 in group B were significantly increased (P <0.01 or P <0.05) 5 and IL-13 levels and IFN-γ / IL-4 ratio increased (P <0.05), while the airway inflammation in mice was significantly reduced. However, there was no significant difference between the above indexes in group D and group B ). Conclusions GATA-3 targeting ODN “trap ” can effectively reduce the production of Th2 cytokines by blocking the activity of GATA-3, thereby reducing the airway inflammation in asthmatic mice.