肌苷对CPZ介导的急性脱髓鞘小鼠行为学及皮质髓鞘的影响

Effect of inosine on behavior and cortex myelin in CPZ mouse model of acute demyelination

目的:探讨肌苷对双环己酮草酰二腙(cuprizone,CPZ)介导的急性脱髓鞘小鼠行为学及皮质髓鞘的影响。方法:在普通饲料中掺入0.2%CPZ,饲养小鼠6 w,同时联合腹腔注射肌苷,制备脱髓鞘治疗模型,利用体重测量、Morris水迷宫、悬尾实验、透射电镜等技术,观察肌苷对脱髓鞘小鼠治疗后行为学及皮质髓鞘的影响。结果:(1)体重变化:与生理盐水对照组比较,CPZ损伤组、肌苷治疗组小鼠体重从第6 d开始均明显降低(P<0.05);(2)行为学:Morris水迷宫空间定位实验中,与CPZ损伤组比较,肌苷治疗组平台象限停留时间明显增加(P<0.05);悬尾实验中,小鼠6 min不动时间均无明显差异(P>0.05);(3)皮质髓鞘电镜观察显示,肌苷治疗组小鼠的皮质髓鞘病理改变程度降低,有新生髓鞘。结论:通过含0.2%CPZ饲料饲养联合腹腔注射肌苷制备脱髓鞘治疗小鼠,可使小鼠的学习、记忆功能明显改善,皮质髓鞘有明显的修复与再生,揭示肌苷对伴有学习记忆功能障碍的脱髓鞘小鼠有髓鞘保护作用。

Objective： To explore the effect of inosine on behavior and cortex myelin in cuprizone（CPZ） mouse model of acute demylination. Methods： C57 BL /6 mice was fed with standard diet that was blended with 0. 2% CPZ,and inosine was injected intraperitoneally to cure acute demyelination for 6 weeks. Morris water maze test,tail suspension test and transmission electron microscope（ TEM） were used to observe learning and memory function and cortex myelin of ice. Results：（1） Weight changes： Weight gain of the CPZ injury group and the inosine treatment group significantly less than that of the saline control group from the sixth day（ P〈 0. 05）,（ 2） Behavioral changes： Morris water maze test showed that escape latency in navigation test of the inosine treatment group was significantly longer than that of the CPZ injury group（ P〈 0. 05）, The tail suspension test showed that the immobility time was no significant differences in the groups.（3） TEM observation ： Compared with the CPZ injury group,the degree of abnormalities structural of myelin was reduced,and there were a lot of new myelin sheaths. Conclusion： Simultaneous administration of inosine effectively attenuated cuprizone induced demyelination,and impoved the learning and memory function,and the remyelination of cortex was obvious. These results suggest that inosine exerts protective effect on demyelination in CPZ mouse model.