地塞米松对实验性自身免疫性脑脊髓炎小鼠IL-17表达的影响

摘要

Objective To explore the effect of dexamethasone on the expression of IL-17 in the brain and spinal cord of mice with experimental autoimmune encephalomyelitis (EAE).Method C57BL/6 mice were randomly divided into three groups:control group,EAE group and dexamethasone group.Mice in EAE and dexamethasone groups were immuned with MOG35-55.Mice in dexamethasone group were administered with 0.07mg·kg-1 dexamethasone by intraperitoneal injection every other day from immunity to death.The morbidity and clinical signs were observed daily.The pathological changes,expression of IL-17,level of IL-17 mRNA and proportion of Th17 cells were observed by HE staining,immunohistochemistry staining,qRT-PCR and flow cytometry respectively.Results Compared to the EAE group,the mobility and mean clinical score of the mice in the dexamethasone group were significantly lower (P＜0.05).Compared with the control group,the inflammation cells in the brain and spinal cord of mice in the EAE group increased significantly (P＜0.05);the number of IL-17 positive cells in the brain and spinal cord,the level of IL-17mRNA in the spinal cord,and the proportion of Thl7 cells in the spleen of mice increased significantly (P＜0.05).Compared to the EAE group mice,the data mentioned above in the dexamethasone group decreased significantly (P＜0.05).Conclusion Dexamethasone can efficiently decrease the mobility,the mean clinical score,the number of inflammation cells and IL-17 positive cells in the brain and spinal cord,the level of IL-17 mRNA in the spinal cord and the proportion of Th17 cells in the spleen.The neuroprotective effect of dexamethasone may be realized by the immunomodulatory mechanism involving inhibiting the axis of IL-17/IL-23.%目的 研究地塞米松对实验性自身免疫性脑脊髓炎(EAE)小鼠脑及脊髓组织中IL-17表达水平及脾组织中Th17细胞比例的影响.方法 将33只C57BL/6小鼠随机分为对照组、EAE组和地塞米松组.EAE组及地塞米松组小鼠以MOG35-55进行免疫造模.地塞米松组小鼠自免疫当天至处死,隔日给予地塞米松磷酸钠注射液0.07mg·kg-1腹腔注射.对照组及EAE组给予等量生理盐水.观察小鼠的发病情况及神经功能评分.应用苏木精-伊红染色、免疫组织化学染色、实时定量PCR、流式细胞学方法分别检测小鼠中枢神经系统炎症细胞浸润、IL-17阳性细胞表达、IL-17mRNA水平及脾组织Th17细胞比例.结果 地塞米松组与EAE组比较,小鼠发病率及神经功能评分明显降低(P＜0.05).与对照组比较,EAE组小鼠脑及脊髓组织中炎性病灶数明显增多(P＜0.05),IL-17阳性细胞数明显增多(P＜0.05),脊髓组织中IL-17mRNA水平明显升高(P＜0.05),脾组织Th17细胞比例明显升高(P＜0.05);与EAE组相比较,地塞米松组小鼠脑、脊髓及脾组织中上述指标明显降低(P＜0.05).结论 地塞米松可以降低EAE小鼠发病率,减轻发病时神经功能损伤程度以及脑和脊髓内炎性细胞浸润程度,并使IL-17mRNA、蛋白表达水平及Th17细胞比例下降.其神经保护作用可能是通过抑制IL-17/IL-23轴等免疫调节机制而实现.