咖啡因慢性干预对小鼠实验性自身免疫性脑脊髓炎影响的观察

目的：探讨不同剂量咖啡因慢性干预对小鼠实验性自身免疫性脑脊髓炎（EAE）的影响及其分子免疫学机制。方法：C57BL／6小鼠随机分为CFA阴性对照组，EAE阳性对照组，咖啡因饮水干预组（1mg·k-1，10mg·kg-1，30mg·kg-1）。使用髓鞘少突胶质细胞糖蛋白35-55（MOG35-55）抗原诱导小鼠EAE模型，咖啡因干预至EAE造模后第20天与对照组小鼠同期处死为止。观察小鼠行为学变化、中枢炎症细胞浸润和损害程度、检测中枢细胞因子IL-17、IFN—γ、TGF—β的mRNA表达含量。结果：咖啡因干预组，特别是30mg·kg-1组的病情严重程度减轻，中枢炎症细胞浸润程度下降，促炎因子表达降低，抑炎因子表达上升。结论：慢性咖啡因干预，可通过降低促炎因子的表达，升高抑炎因子的表达，减轻小鼠EAE的炎症损伤。

Effect of Chronic Treatment of Caffeine on the Mice Model of Experimental Autoimmune Encephalomyelitis

Aim： To investigate the effect of treatments with different doses of caffeine on mice experimental autoimmune encephalomyelitis （EAE） and the underlying mechanism. Methods： C57BL/6 mice were randomly divided into five groups： CFA control group, EAE positive group and caffeine treatment groups （divided into 1 mg-kg~, 10 mg-kg-~ and 30 mg.kg-1 subgroups）. For the caffeine treatment groups, they were administrated different doses of caffeine for 10 days, and then EAE model was made by using means of immune reactivity to myelin oligodendrocyte glycoprotein（MOG35-55）. After immunization, the mice of caffeine treatment groups were continuously administrated different doses of caffeine for 20 days. The behavioral and pathological changes were observed, and the infiltration of inflammatory cells and the damage in CNS were examined by HE staining. The expressions of cytokines such as IL-17、IFN-γ and TGF-β mRNAs in CNS were quantified by RT-PCR. Results： The EAE mice of caffeine treatment groups, especially the mice administrated caffeine for 30 mg.kg-1, not only the degree of disease severity was obviously ameliorated, but also the infiltration of inflammatory cells in CNS was decreased moderately. In addition, the expressions of inflammatory factors IL-17 and IFN-γ mRNAs were down-regulated, and the expression of anti-inflammatory factor TGF-β mRNA was up regulated. Conclusion： Long-term caffeine treatment could moderate the damage of inflammation on EAE mice by the down-regulating of IL-17 and IFN-γ mRNAs expressions and the up-regulating of TGF-β mRNA expression.