地塞米松对实验性自身免疫性脑脊髓炎小鼠髓鞘保护作用的研究

目的:分析地塞米松对实验性自身免疫性脑脊髓炎(EAE)小鼠炎症反应、髓鞘脱失及髓鞘再生的影响,探讨地塞米松治疗多发性硬化的新作用。方法:应用MOG35-55免疫C57BL/6小鼠建立EAE模型。小鼠随机分为正常对照组、EAE组及地塞米松组,观察各组临床症状;采用HE染色、LFB染色、透射电镜扫描及免疫组化染色方法,检测免疫后第13、20、30 d各组小鼠脊髓组织炎症反应、髓鞘脱失及髓鞘再生情况。结果:地塞米松显著降低EAE小鼠发病率、延缓起病时间、减轻疾病严重程度。各个时间点地塞米松组脊髓组织炎性细胞浸润、髓鞘脱失及轴索变性程度较EAE组明显减轻。免疫后第20、30 d,EAE组Olig2阳性细胞数较正常对照组明显增加;免疫后各时间点,地塞米松组Olig2阳性细胞数较正常对照组均明显增加,第13、20 d较EAE组明显增加。结论:地塞米松可增加脊髓组织Olig2表达、促进髓鞘再生,这可能为地塞米松治疗EAE及多发性硬化的效应途径。

Protective effect of dexamethasone on myelin sheath in mice with experimental autoimmune encephalomyelitis

Objective: To investigate the potential novel therapeutic targets of dexamethasone on multiple sclerosis by analyzing the effects of dexamethasone on the inflammatory responses,demyelination and remyelination in mice with experimental autoimmune encephalomyelitis(EAE).Methods:C57BL/6 mice were randomly divided into control group,EAE group and dexamethasone group.The latter two groups were immunized with MOG35-55 and clinical symptoms were observed.The inflammatory responses,demyelination and remyelination in the spinal cords of mice were detected by HE staining,LFB staining,electron microscopy and immunohistochemisty on day 13,20 and 30 post immunization.Results:Treatment with dexamethasone significantly lowered the morbidity,delayed the onset time and inhibited the severity of EAE in mice,accompanied by mitigating inflammatory infiltration,demyelination and axonal degeneration in the spinal cords of mice.Compared with the control group,the numbers of Olig2 immunopositive cells significantly increased in the spinal cords of the EAE group on day 20 and 30 post immunization.In the dexamethasone group,the numbers of Olig2 immunopositive cells in the spinal cords were higher than those in the control group at each time point and higher than those in the EAE group on day 13,20 post immunization.Conclusions: Dexamethasone could increase the expression of Olig2 and promote remyelination,which may be one protetive effect mechanism involved in treatment of EAE or multiple sclerosis.