神经节苷脂钠侧脑室注射对脑性瘫痪模型大鼠学习记忆能力的影响

Effect of injection of ganglioside sodium into cerebral ganglion on the behavior of model rats with cerebral palsy

目的观察侧脑室注射神经节苷脂钠对脑性瘫痪(CP)模型大鼠学习记忆能力的影响,探讨其治疗脑瘫的可能机制。方法SD大鼠36只,分为空白对照组、模型组和神经节苷脂钠组(n=12),采用手术切除大脑皮质和部分大脑组织的方法建立大鼠脑瘫动物模型。用大鼠脑定位仪侧脑室注射神经节苷脂钠给药3次(每10 d一次,注射3次),用水迷宫仪进行定位航行和空间探索实验学习记忆能力改变,悬吊试验和斜坡试验比较大鼠运动改变,并测定治疗前后脑组织液钙调蛋白(Calmodulin,CaM)及钙调蛋白依赖性蛋白激酶Ⅱ(Ca/calmodulin-dependent protein kinases or CaM kinasesⅡ,CaMKⅡ),以研究神经节苷脂钠影响CP大鼠学习记忆能力的机制。结果神经节苷脂钠组大鼠水迷宫中找到平台时间、斜坡试验时间显著缩短;悬吊试验时间、大鼠在第一象限和中环停留时间明显延长;定位航行中潜伏期和游泳距离缩短,脑组织液CaMl及CaMKⅡ增高,与模型组比较,P<0.05。结论神经节苷脂钠能促进CP大鼠学习记忆能力,其作用机制可能与神经节苷脂钠抑制CaM及CaMKⅡ合成,阻断Ca^(2+)/CaM-CaMKⅡ信号传导通路,促进脑能量代谢,并抑制神经细胞膜钙内流和钙蛋白水解达到修复受损中枢神经,进而改善CP大鼠脑缺血缺氧状态并促进受损神经再生和神经组织功能的恢复。

Objective To observe the effect of injection of sodium in the lateral ventricle on the neurological behavior in rats with cere-bral palsy,and explore the possible mechanism of the treatment of cerebral palsy. Methods Thirty six SD rats were randomly divided into control group,model group and treatment group（ n = 12） . The method of surgical resection of cerebral cortex and part of brain tissue was used to establish animal model of cerebral palsy in rats. Ganglioside sodium was injected in lateral ventricle three times by rat brain locator （once every 10 days for 30 days）. The water maze testing apparatus for place navigation and space assay were performed to ex-plore the changes in learning and memory. Suspension test and the test for slope is carried out to evaluate the change of motion. The lev-el of anterior brain tissue fluid calmodulin （ CaM） and calmodulin dependent protein kinase II （ CaMK II ） were evaluated explore the mechanism of ganglioside sodium effect in cerebral palsy rats learning memory. Results The duration of finding the platform in Morris water maze, slope test time of treatment group was significantly reduced ; suspension, stay in first quadrant and central residence time was significantly prolonged ; the latency and swimming distance in place navigation was shortened. The brain tissue CaM and CaMK H in-creased, compared with the model group,P 〈0.05. Conclusion Ganglioside sodium can promote learning and memory ability of cere-bral palsy rats,which may correlated with ganglioside sodium down-regulating expression of CaM and CaM II mRNA,blocking Ca2 ＋ / CaM-CaMK II signal transduction pathway,promoting brain energy metabolism and inhibiting nerve cell membrane calcium current and calcium protein hydrolysis to repair the damaged central nervous system （CNS） ,thus to regenerate the injured nerve and improve the cerebral palsy rats cerebral ischemia and hypoxia and the restoration of nerve function.