【摘要】 目的研究血管性痴呆(VD)大鼠海马N-甲基-D-天冬氨酸-2B亚基受体(NR2B)水平和钙/钙调蛋白依赖性蛋白激酶Ⅱ(CaMKⅡ)活性的变化以及美金刚的干预作用。方法采用结扎双侧颈总动脉方法制备VD大鼠模型,随机分为VD模型组(VD组)和美金刚治疗组(美金刚组)。于术后4周、8周、12周、16周用Morris水迷宫试验检测VD组和美金刚组大鼠的学习记忆水平,用RT-PCR法检测大鼠海马NR2B水平,用32P掺入法检测大鼠海马CaMKⅡ的活性;并与假手术组比较。结果与假手术组比较,VD组大鼠术后各时间点的学习记忆能力均显著下降(均P<0.01);海马NR2B的水平术后4周时明显增高(P<0.05),术后8～16周显著降低(均P<0.01);海马总CaMKⅡ活性术后4周时明显增高(P<0.01),术后8周下降,术后12周、16周明显降低(均P<0.01)。美金刚组术后4周时上述3项检测结果与VD组比较,差异均有统计学意义(均P<0.01),而与假手术组比较,差异均无统计学意义;在其他时间点,与假手术组比较,差异有统计学意义(P<0.05～0.01);学习记忆水平和NR2B水平术后8周、12周明显高于VD组(P<0.01～0.05);总CaMKⅡ活性与VD组比较,差异无统计学意义。结论VD大鼠海马NR2B水平和总CaMKⅡ活性降低;美金刚能上调海马NR2B表达及改善VD大鼠的认知功能,但对CaMKⅡ活性的影响有限。更多还原

【Abstract】 Objective To investigate changes of N-methyl-D-aspartic acid receptor 2B(NR2B) level and calcium/calmodulin-dependent protein kinase Ⅱ(CaMK Ⅱ) activities in the hippocampus of vascular dementia(VD) rats and the intervention effects of Memantine.Methods The VD rat models were established by permanent,bilateral occlusion of the common carotid arteries.The rats were randomly divided into VD group and Memantine-treated group.At 4,8,12,16 weeks after operation,the water maze test was performed to detect the ability of learning and memory of the rats.The changes of NR2B level were measured by RT-PCR.The changes of the CaMK Ⅱ activities were determined by incorporation of 32P into histone.The resoults were compared with the sham-operated group.Results Compared with the sham-operated group,the ability of learning and memory of VD group rats at each time point after operation decreased significantly(all P<0.01);the level of NR2B increased significantly at 4 weeks after operation(P<0.05)and decreased at 8～16 weeks after operation(all P<0.01).Total CaMK Ⅱ activity increased significantly at 4 weeks after operation(P<0.01),then dropped at 8 weeks after operation,and decreased significantly at 12,16 weeks after operation(all P<0.01).In Memantine-treated group,at 4 weeks after operation,there were statistical differences in the indexes mentioned above in contrast with the VD group(all P<0.01),and no statistical differences with the sham group.However,at other time point,there were significant differences with sham group(P<0.05～0.01).Moreover,the ability of learning and memory and the level of NR2B were greatly better than those of VD group(P<0.05～0.01) at 8,12 weeks after operation but totle CaMK Ⅱ activitiy were similar to those of VD group.Conclusions NR2B level and CaMK Ⅱ activities in the hippocampus of VD rats decrease and Memantine can improve VD rat’s recognition by modulating the expression of NR2B,but its effect on CaMK Ⅱ activities is limited.更多还原