盐酸多奈哌齐对血管性痴呆大鼠海马CA1区神经细胞凋亡及NMDAR-2B表达的影响

摘要

目的 观察盐酸多奈哌齐治疗的血管性痴呆(VD)大鼠海马CA1区神经细胞凋亡及N-甲基-D-天门冬氨酸受体2B(NMDAR-2B)的变化,探讨其在VD治疗中的作用机制.方法 采用永久性结扎双侧颈总动脉法制作大鼠VD模型,将120只SD大鼠随机分为假手术组、手术对照组、药物治疗组各40只,每组分别在1个月和2个月处死20只大鼠,应用Morris水迷宫检测大鼠的学习记忆能力,用免疫组化染色方法 检测大鼠海马CA1区NMDAR-2B表达,用TUNEL染色检测神经细胞凋亡.结果 治疗组大鼠学习记忆能力明显高于手术对照组,海马CA1区NMDAR-2B表达明显高于手术对照组,海马区神经细胞凋亡明显少于手术对照组(P均＜0.01);与假手术组比较均无统计学差异(P＞0.05).结论 盐酸多奈哌齐能上调VD大鼠海马CA1区NMDAR-2B表达,减轻EAA的毒性作用,保护神经细胞,有助于增强和调节学习记忆能力.%Objective To investigate the mechanism of action of donepezil in vascular dementia by study the change of N-Methyl-D-aspartate 2B receptor expression and neurons apoptosis in hippocampal CA1 of vascular dementia rats. Methods 120 SD rats were randomly devided into three groups: sham operation group,VD model group and Donepezil treated group, with 40 cases in each. The VD model. was estalished by occlusion of the bilateral common carntid arteries. 20 rats of each group were sacrificed at 1 month and 2 months post operation. The water maze test was performed to examine the ability of learning and memory of the rats, the expression of NMDAR-2B in hippocampal CA1 was measured by immunohisto-chemical staining and neurons apoptosis was observed with terminal deoxynucleotidyl transferase mediated dUTP-biotin nick end labeling(TUNEL) staining. Results In comparison with VD model group, the ability of learning and memory were better in donepezil treated group; the expression of NMDAR-2B in hippocampal CA1 increased significantly ( P ＜ 0.01 );neurons apoptosis in hippocampal decreased significantly (P ＜0.01 ). Donepezil treated group had no statistical difference in all of the ability of learning and memory, expression of NMDAR-2B and neurons apoptosis compared with the sham operation group. Cobclusion Donepezil is able to reduce the toxic effects of EAA, safeguard neurons and impair 1earning and memory ability in upregulate expression of NMDAR-2B in hippocampal CA1 of VD rats.