【摘要】 目的研究美金刚对脑缺血再灌注小鼠模型ERK、CREB信号通路及突触可塑性的作用机制。方法60只小鼠随机分为假手术组(Sham),模型组(MCAO),美金刚20 mg/kg组(M20),美金刚4 mg/kg组(M4),生理盐水组(NS),除假手术组外,其余4组均使用线栓法建立小鼠大脑中动脉梗死模型,观察小鼠的体重变化及神经功能缺损程度,甲酚紫染色观察小鼠脑萎缩体积,粘附物去除实验观察缺血小鼠的运动及感觉功能变化,Morris水迷宫检测小鼠的认知记忆功能,Western Blot检测ERK1/2、p-ERK1/2、CREB、p-CREB、PSD-95、Synaptophysin等蛋白的表达情况。结果与模型组(MCAO)、美金刚4 mg/kg组(M4)及生理盐水组(NS)相比,美金刚20 mg/kg组的小鼠体重下降程度减小,神经功能缺损评分下降,脑萎缩体积减轻,小鼠感觉运动功能出现改善,水迷宫实验结果提示学习记忆损伤程度减轻,p-ERK1/2、p-CREB、PSD-95、synaptophysin等蛋白表达升高。结论小鼠脑缺血后持续给予美金刚20 mg/kg治疗,可以提高小鼠的神经功能恢复,改善小鼠的学习记忆功能,改善了大脑的突触可塑性。更多还原

【Abstract】 Objective To investigate the mechanism of memantine on ERK/CREB signaling and synaptic plasticity in a mouse model of cerebral ischemia-reperfusion. Methods Sixty mice were randomly divided into a sham operation group( Sham),middle cerebral artery occlusion model group( MCAO),20 mg/kg memantine group( M20),4 mg/kg memantine group( M4),and saline group( NS). With the exception of the Sham group,ischemia-reperfusion was established in groups using a suture to achieve MCAO. Changes in body weight and degree of neurological deficits were observed in the mice. Brain atrophy volume was measured using cresyl violet staining,while sensorimotor function was observed by an adhesive removal test and cognitive function was detected by Morris water maze. Expression of ERK1/2,phosphorylated ERK1/2( p-ERK1/2),CREB,p-CREB,postsynaptic density protein 95( PSD-95) and synaptophysin were detected by western blot assay. Results Compared with MCAO,M4,and NS groups,the M20 group exhibited reduced weight loss,decreased neurological severity scores,decreased volume of brain atrophy,and improved sensorimotor function. In addition,the results of water maze testing showed that the degree of learning and memory impairment was reduced in the M20 group. Expression of p-ERK1/2,p-CREB,PSD-95,and synaptophysin proteins were increased in the M20 group compared with other groups. Conclusions Continuous treatment with memantine( 20 mg/kg) after cerebral ischemia in mice can improve the recovery of neurological function,ameliorate deficits in learning and memory,and improve synaptic plasticity of the brain.更多还原