一氧化氮供体对实验性自身免疫性脑脊髓炎的作用

Effect of 3-morpholinosydnonimine on experimental autoimmune encephalomyelitis

目的探讨一氧化氮供体3-吗啉-斯德酮亚胺（3-morpholinosydnonimine,SIN-1）对实验性自身免疫性脑脊髓炎（experimental autoimmune encephalomyelitis,EAE）大鼠的作用。方法应用豚鼠髓鞘碱性蛋白68-86（myelin basic protein 68-86,MBP68-86）主动免疫制作EAE实验动物模型。将大鼠随机分为SIN-1组和对照组,SIN-1组大鼠于致敏后第0~7天给予SIN-1药物干预,动态观察两组大鼠的临床症状及体质量变化,致敏后第14天采用ELISA方法检测各组大鼠单个核细胞（mononuclear cells,MNC）培养上清中γ干扰素（IFN-γ）和白细胞介素-4（IL-4）水平,并观察大鼠脑组织病理变化。结果与对照组比较,SIN-1组大鼠发病时间延迟,恢复时间提前,体质量明显增加,临床症状明显减轻;疾病症状最高评分明显降低。SIN-1组大鼠MNC培养上清中IFN-γ水平为（90.29±9.07）pg/mL,较对照组的（121.57±10.44）pg/mL明显降低（P〈0.05）;IL-4水平为（18.14±3.98）pg/mL,较对照组的（8.14±1.95）pg/mL明显增加（P〈0.05）。SIN-1组大鼠组织病理损伤较对照组明显减轻。结论一氧化氮供体SIN-1可抑制EAE大鼠病情发展,对EAE具有保护作用。

Objective To investigate the effect of nitric oxide donor 3-morpholinosydnonimine（SIN-1）on experimental autoimmune encephalomyelitis（EAE）in Lewis rats.Methods EAE was induced by immunization with myelin basic protein 68-86 in Lewis rats.All rats were divided into the SIN-1 group and the control group randomly.SIN-1 was given after the sensitization,starting on the day of sensitization and continued for another 7 days in the SIN-1 group.The clinical symptoms,the body weight changes,pathology changes of brain were observed in two groups.The levels of IFN-γ and IL-4 in cultured supernatant of mononuclear cells（MNC） in each group were detected by ELISA at the 14th day after sensitization.Results Compared with the control group,the onset of EAE in SIN-1 group was delayed,while the recovery appeared earlier,the weight increased obviously,the clinical symptoms relieved and the maximal clinical score reduced in the SIN-1 group.The level of IFN-γ in cultured supernatant of MNC in the SIN-1 group（90.29±9.07）pg/mL was lower than that in the control group（121.57±10.44）pg/mL（P0.05）,while the level of IL-4（18.14 ±3.98）pg/mL was significantly higher than that in the control group（8.14±1.95）pg/mL（P0.05）.The pathological damage of EAE in the SIN-1 group attenuated significantly comparing with the control group.Conclusions SIN-1 can inhibit the progression of EAE in rats,and have protective effect on EAE rats.The mechanism may be related to the balance of Th1/Th2 type cytokines.