侧脑室注射神经节苷脂钠对脑瘫模型大鼠学习记忆能力的影响

目的 探讨神经节苷脂钠(GM)侧脑室注射对脑瘫模型大鼠学习记忆能力的机制,为临床治疗脑瘫提供理论依据.方法 将36只SPF级SD大鼠随机分为对照组、模型组和GM组.模型组和GM组大鼠通过切除大脑皮质及部分脑组织建模.成模后1d、10d、20 d、30 d用大鼠脑定位仪经大鼠侧脑室注射GM给药.在成模后和未次给药后用水迷宫仪进行空间探索实验、定位航行、悬吊、斜坡等实验,比较大鼠学习记忆能力及运动能力改变,并采用ELISA测定脑海马区乙酰胆碱(Ach)及眶静脉血乙酰胆碱脂酶(AChE)活性;脑组织液钙调蛋白依赖性蛋白激酶Ⅱ(CaMKⅡ)及钙调蛋白(CaM).结果 与模型组比较,GM组大鼠治疗后找到平台时间及斜坡实验时间显著缩短;悬吊时间、第一象限和中环停留时间明显延长;定位航行中潜伏期、游泳距离缩短,脑海马区Ach含量降低、AChE活性增强;脑组织液CaMKⅡ及CaM增高(P＜0.05).结论 GM可明显抑制脑瘫模型大鼠脑组织液CaMKⅡ和CaM合成,降低神经细胞钙蛋白水解和钙内流,并通过阻断CaMKⅡ这一信号传导通路,提高AChE活性,抑制Ach释放来降低大鼠因脑缺血缺氧对中枢神经造成的损伤,使受损脑神经纤维修复和再生,进而促进中枢神经纤维功能恢复来提高学习记忆能力.

Effect of Lateral Ventricle Injection of Ganglioside Sodium on Learning and Memory in Rats with Cerebral Palsy

Objective To study the mechanism of Ganglioside (GM) lateral ventricle injection on learning and memory ability of rats with cerebral palsy,and to provide theoretical basis for clinical treatment of cerebral palsy.Methods Thirty-six SPF rats were randomly divided into blank control group,model group and GM group.The model group and GM group were randomly divided into the model group and the SD group.After modeling,1 days and 10,20,30 days with the brain localization of rat instrument by rat intracerebroventricular injection of GM administered after modeling and administration after the water maze experiment instrument to explore,navigation,suspension and slope experiments comparing the ability of learning and memory of rats and exercise the ability to change space.And using the ELISA method for the determination of acetylcholine in hippocampus (Ach) and orbital venous blood acetylcholinesterase (AChE) activity.Determination of brain tissue and calmodulin dependent protein kinase Ⅱ (CaMKⅡ) and calmodulin (CaM).Results Compared with the model group,the rats in group GM after treatment,the time of finding the platform and slope experiment time was significantly shortened,suspension time,the first quadrant and the residence time in the voyage prolonged;positioning latency,swimming distance shortened,the Ach level was decreased,and AChE activity was increased.the brain tissue of liquid CaMK and CaM increased (P＜0.05).Conclusion In rat cerebral palsy model,GM could inhibit the synthesis of CaMKⅡ and CaM,reduce hydrolysis of neuronal calcium protein and calcium influx.By blocking the signaling pathway of CaMKⅡ,GM treatment increases the activity of Ach,reduces brain damage caused by cerebral ischemia and hypoxia,thus promoting repair and regeneration of lesioned nerves and subsequently learning and memory.