N-甲基-D-天冬氨酸受体和突触后致密物质95在血管性痴呆大鼠中作用机制的研究

The mechanism of action of NR2B/PSD-95 in the vascular dementia rats

目的观察血管性痴呆(VaD)大鼠N-甲基-D-天冬氨酸-2B亚基受体(NR2B)和突触后致密物质95(PSD-95)在VaD发生、发展中的作用。方法采用永久性结扎双侧颈总动脉方法将96只Wistar大鼠随机分为假手术组(32只)、VaD模型组(模型组,32只)和美金刚治疗组(治疗组,32只)。用免疫组织化学法检测术后4、8、12、16周大鼠海马NR2B和PSD-95的表达,并同时采用Morris水迷宫测试大鼠的学习记忆水平。结果随着缺血时间的延长,与假手术组比较,模型组大鼠术后4、8、12、16周学习记忆能力下降,差异显著(P<0.01);术后4周时NR2B和PSD-95的表达明显高于假手术组(P<0.01),此后逐渐减少,显著低于假手术组(P<0.01),术后16周时表达最少。治疗组大鼠术后4周时学习记忆水平及NR2B、PSD-95的表达与假手术组比较无显著差异,术后8、12、16周时,上述指标较模型组显著好转但仍差于假手术组(P<0.05,P<0.01)。结论大鼠海马NR2B和PSD-95作为复合体参与VaD的形成和发展,适量的美金刚通过调节NR2B的表达进而改善VaD大鼠的认知功能。

Objective To investigate the role of N-methyl-D-aspartic acid receptor 2B（NR2B） and postsynaptic density 95（PSD-95） in development of vascular dementia（VaD） of rats. Methods The VaD rat model was established by permanent occlusion of bilateral common carotid arteries. One hundred and twenty-eight Wistar rats were randomly divided into sham operation group,VaD model group and memantine-treated group. The water maze test was used to test the ability of learning and memory of the rats and the changes of the expression of NR2B and PSD-95 in hippocampus were measured by immunohistochemical staining. Results The ability of learning and memory of VaD rats decreased significantly compared with the sham operation rats （P d0.01）. NR2B and PSD-95 had the similar expression in VaD rats, which first increased greatly （P〈0.01） ,then fell and was significantly different from that in the sham operation group （P〈0.01）. In memantine-treated group, at 4 weeks after operation, the rats presented no statistical difference in learning and memory level and the expression of NR2B and PSD-95 as compared with the sham operation group. However,at 8,12,16 weeks after operation, the indexes mentioned above were better than those in VaD rats and still worse than those in the sham operation group （P〈0.05, P〈0.01）. Conclusion NR2B and PSD-95 are involved in the development of VaD and memantine can improve recognitive function by modulating the expression of NR2B.