高同型半胱氨酸血症对实验性变态反应性脑脊髓炎小鼠的影响

Investigation of relationship between hyper-homocysteinemia and experiment autoimmune encephalomyelitis mice

目的:观察高同型半胱氨酸血症(HHcy)对实验性变态反应性脑脊髓炎(EAE)小鼠的影响,探讨HHcy在多发性硬化(MS)中的意义。方法:饮水中添加4%蛋氨酸使C57BL/6鼠具有HHcy,以MOG35-55肽段免疫C57BL/6鼠制备EAE模型,分别产生四组观察对象:普通喂养的正常鼠和EAE鼠(HC组和EAE组),添加蛋氨酸辅食的小鼠和EAE鼠(HC+Hcy组和EAE+Hcy组)。制模后3周内的不同时间段,评估各组小鼠症状,测定血清Hcy水平;3周后比较各EAE组小鼠细胞TNF-α、IFN-γ和IL-17因子水平。结果:EAE和HC组小鼠血清Hcy浓度无显著统计学差异(P>0.05);EAE+Hcy组小鼠临床症状评分和体重减轻均较EAE组严重(P<0.05);EAE+Hcy组小鼠TNF-α和IFN-γ水平显著高于EAE组(P<0.05),而IL-17水平在两组中无显著统计学差异(P>0.05)。结论:EAE疾病过程中Hcy水平无明显升高,但HHcy可加重EAE的临床症状,其机理同Hcy促进TNF-α和IFN-γ细胞因子产生有关,而与IL-17无关。

Objective：To investigate the relationship between hyper-homocysteinemia （ HHcy） and experiment autoimmune en-cephalomyelitis （EAE） mice,and to study the cause and effect of HHcy in multiple sclerosis （MS）.Methods： Four groups were included in this study：healthy C57BL/6 mice and EAE mice fed with chow（HC and EAE group）,healthy mice and EAE mice supple-mented with 4%（w/v） methionine in the drinking water （HC＋Hcy and EAE＋Hcy group）.Clinical symptoms,the levels of Hcy and cytokines （ TNF-α,IFN-γand IL-17） were evaluated at different time points.Results：EAE group had no greater Hcy than HC group （ P〉0.05 ）.The clinical scores and weight loss of mice from EAE＋Hcy group were more severe than those from EAE group during the course of EAE （ P〈0.05 ）.EAE＋Hcy group had higher levels of TNF-αand IFN-γthan EAE group （ P〈0.05 ） ,while IL-17 was about the same.Conclusion：Mice do not have gradually increased Hcy during the course of EAE.HHcy worsen the symptoms of EAE by pro-moting the production of TNF-αand IFN-γ,but not IL-17.