不同剂量美金刚对慢性脑缺血老龄大鼠认知障碍的改善作用及机制  

Protective effects and mechanism of different doses of memantine on cognitive impairment in aged rats with chronic cerebral ischemia

作　　者：李莹[1] 杨友华[1] 黄丹[1] 陈晓青[1] 易卉玲[1] 舒细记[1] 柳威[1] 

机构地区：[1]江汉大学,湖北武汉430056

出　　处：《中国医院药学杂志》2016年第18期1546-1550,共5页Chinese Journal of Hospital Pharmacy

基　　金：湖北省自然科学基金(编号:2015CFB561)

摘　　要：目的:探讨美金刚(Memantine)对慢性脑缺血老龄大鼠认知障碍及海马区神经的保护作用及机制。方法:采用双侧颈总动脉结扎法(2VO)建立慢性脑缺血动物模型,将造模成功的31只12月龄雄性SD大鼠随机分为缺血组(n=7)和干预组(3.75,7.5,15,30 mg·kg-1,n=6),对照组(n=5)只分离血管不做结扎处理。采用水迷宫评估大鼠空间学习记忆功能,免疫荧光染色后对海马齿状回神经细胞增殖及CA1区凋亡细胞进行计数。结果:水迷宫实验显示:缺血组大鼠空间学习和记忆能力明显受损,与对照组和干预组相比有统计学差异(P<0.01),美金刚干预后大鼠的空间学习和记忆能力得以改善(P<0.05)。免疫荧光染色显示:缺血组大鼠新生神经细胞计数明显多于对照组(P<0.01),干预组齿状回新生神经细胞数量较对照组进一步增多(P<0.01);缺血组大鼠凋亡细胞明显多于对照组(P<0.01),美金刚干预后凋亡细胞数量较缺血组明显减少(P<0.05)。相关性分析表明,CA1区凋亡细胞数量与空间记忆功能呈负相关。结论:美金刚可通过促进海马神经细胞增殖、抑制细胞凋亡,改善认知功能障碍,且不同的药物剂量作用效果存在差异。OBJECTIVE To study protective effects and mechanism of memantine on cognitive impairment in aged rats with chronic cerebral ischemia.METHODS Bilateral common carotid artery occlusion（2VO）was used to establish chronic cerebral ischemia model.Thirty six male-SD aged rats were randomly divided into ischemia group（n=7）,control group（n=5）and four different doses of memantine groups（3.75,7.5,15,30 mg·kg-1,6 per group）.For rats in control group,blood vessels were only split without occlusion.Spatial learning and memory were accessed by Morris Water Maze,double labeled immunofluorescence was used to study neurogenesis in dentate gyrus and neuron apoptosis in CA1 region.RESULTS Spatial learning and memory of ischemia group were obviously impaired compared to control group and memantine group（P〈0.01）.Memantine treatment significantly ameliorated spatial learning and memory impairment of ischemia rats（P〈0.05）.New born neurons of ischemia group were significant more than those of control group（P〈0.01）,memantine 7.5 mg·kg-1 and 15 mg·kg-1 increased new born neurons in hippocampal dentate gyrus（P〈0.01）.Apoptotic cells of ischemia group were more than control group（P〈0.01）,and rats treated with 7.5 mg·kg-1（P〈0.01）and 15 mg·kg-1（P〈0.05）memantine decreased apoptotic neurons in hippocampal CA1 region.Number of apoptosis cells was negatively correlated to spatial memory.CONCLUSION Memantine resists cognition impairment by promoting neurogenesis and inhibits apoptosis in hippocampus,with variation between different doses.

关 键 词：慢性脑缺血 美金刚 认知 凋亡 老龄鼠 

分 类 号：R285.5[医药卫生—中药学]