美金刚对血管性痴呆大鼠海马N-甲基-D-天冬氨酸-2B受体的影响

Effect of memantine on NMDAR-2B in hippocampus of vascular dementia rats

目的观察经美金刚治疗的血管性痴呆(VaD)大鼠海马N-甲基D-天冬氨酸-2B受体(NMDAR-2B)的变化,并探讨其在VaD中的作用机制。方法采用永久性结扎双侧颈总动脉方法制备VaD大鼠模型,将128只Wistar大鼠随机分为假手术组、VaD模型组和美金刚高、低剂量治疗组,每组32只,各组分别于术后4、8、12、16周处死8只大鼠。用Morris水迷宫衡量大鼠学习记忆水平,用免疫组织化学法检测大鼠海马NMDAR-2B的表达。结果随缺血时间延长,VaD模型组大鼠的学习记忆能力下降,与假手术组比较有显著性差异(P<0.01);NMDAR-2B的表达在缺血4周时明显高于假手术组(P<0.01),此后逐渐减少,并显著低于假手术组(P<0.01),缺血16周时表达最少。学习记忆水平及NMDAR-2B的表达美金刚高、低剂量治疗组在缺血4周时与假手术组比较无显著性差异,在缺血8、12、16周时,美金刚高剂量治疗组较VaD模型组显著好转但仍低于假手术组(P<0.01,P<0.05),美金刚低剂量治疗组与模型组无显著差异但明显低于假手术组(P<0.05,P<0.01)。结论VaD大鼠学习记忆的改变与海马NMDAR-2B变化相关,可用适量的美金刚对NMDAR-2B调节以改善VaD大鼠认知功能。

Objective To investigate the mechanism of action of memantine in vascular dementia by studying the change of N methyl-D aspartate-2B receptor（NMDAR-2B） in hippocampus of vascular dementia rats. Methods 128 Wistar rats were randomly divided into sham operation group, vascular dementia （VaD） model group and memantine groups treated with high or low dose. Eight rats of each group were sacrificed at 4,8,12,16 weeks post operation. The water maze test was performed to examine the ability of learning and memory of the rats and the expression of NMDAR-2B in hippocampus was measured by immunohistochemical staining. Results The ability of learning and memory of VaD rats decreased significantly compared with the sham rats. The ex pression of NMDAR 2B in VaD rats increased greatly first then fell down and was significantly different from that of the sham group. At 4 weeks post operation,both memantine treated groups presented no statistical difference in learning and memory level and the expression of NMDAR-2B compared with the sham group. However,at 8,12,16 weeks post operation,the above two indexes of high dose group were better than those of VaD rats, but still worse than those of the sham group. Conclusion The change of NMDAR-2B was related to the impairment of learning and memory of VaD rats and memantine at adequate dosage improved recognition function by modulating NMDAR-2B.