糖皮质激素对哮喘小鼠CD4^+T细胞中miRNA-155表达调控的研究

Effects of glucocorticoid on miRNA-155 expression in CD4^+ T cells of asthmatic mice

目的:探讨糖皮质激素对哮喘小鼠CD4^+ T细胞中微小RNA-155(miRNA-155)表达调控的影响。方法:使用糖皮质激素对卵清蛋白诱导的小鼠哮喘模型进行治疗,观察糖皮质激素对哮喘小鼠肺组织病理学、肺组织及CD4^+ T细胞中miRNA-155表达和支气管肺泡灌洗液(BALF)中细胞因子含量的影响。结果:RT-qPCR结果显示,哮喘小鼠肺组织和脾脏CD4^+ T细胞中miRNA-155表达显著升高,随着接触过敏原时间的增加,CD4^+ T细胞中miRNA-155水平显著升高(P<0.01)。HE和PAS染色显示,与对照组相比,模型小鼠肺组织中炎性细胞浸润显著增加,给予糖皮质激素治疗后可明显减轻支气管周围和血管周围炎症,减少增生杯状细胞的黏液分泌。糖皮质激素治疗后哮喘小鼠肺组织中的miRNA-155水平显著降低,CD4^+ T细胞中的miRNA-155水平显著下调。糖皮质激素治疗可抑制哮喘小鼠的脾脏中CD4^+ CD8^-细胞比例的增加,减少哮喘小鼠肺组织中CD4^+ T细胞的聚集。糖皮质激素治疗后BALF中白细胞介素4(IL-4)、IL-5和IL-13水平下降,干扰素γ水平显著增加。结论:糖皮质激素可抑制哮喘小鼠肺组织中CD4^+ T细胞的聚集,并可降低肺组织和脾脏中CD4^+ T细胞的miRNA-155的表达。

AIM:To investigate the effects of glucocorticoid on the regulation of microRNA-155(miRNA-155)expression in the CD4^+T cells of asthmatic mice.METHODS:The ovalbumin(OVA)-induced asthma mouse model was established and the mice were treated with glucocorticoid.The effects of glucocorticoid on the pulmpnary histopathological changes,the expression of miRNA-155 in the lung tissues and CD4^+T cells,and the levels of cytokines in the bronchoal-veolar lavage fluid(BALF)were evaluated.RESULTS:The results of RT-qPCR showed that the expressions of miRNA-155 in the lung tissues and CD4^+T cells from the spleen of asthmatic mice were significantly increased,and the level of miRNA-155 in the CD4^+T cells was significantly increased with the increase in the allergen exposure time(P<0.01).HE and PAS staining showed that OVA significantly increased inflammatory cell infiltration as compared with control group,and the peribronchial and perivascular inflammation and mucus secretion of proliferative goblet cells were significantly reduced after glucocorticoid treatment.Glucocorticoid treatment inhibited the increase in the proportion of CD4^+CD8^-cells in the spleen and decreased the accumulation of CD4^+T cells in the lung tissues of asthmatic mice(P<0.01).After glucocorticoid treatment,the levels of interleukin-4(IL-4),IL-5 and IL-13 in BALF were decreased,while the level of interferon-γwas increased significantly(P<0.01).CONCLUSION:Glucocorticoid reduces the accumulation of CD4^+T cells and inhibits the expression of miRNA-155 in the lung tissues and spleen CD4^+T cells of asthmatic mice.