血管性痴呆大鼠N-甲基-D-天冬氨酸-2B受体变化机制的研究

The mechanism of alterations of NMDAR-2B subunit expression in hippocampus of vascular dementia rats

目的研究血管性痴呆(VD)大鼠形成过程中N-甲基D-天冬氨酸-2B受体(NR2B)的变化规律及作用机制。方法永久性结扎双侧颈总动脉制备VD大鼠模型,用Morris水迷宫衡量大鼠的学习记忆水平,用免疫组化法检测大鼠海马NR2B的表达。结果随缺血时间延长,VD大鼠的学习记忆能力下降,缺血4周后与对照有显著差异(P<0.01);NR2B的表达随缺血时间变化,呈先升后降改变,缺血2周时表达最多,与对照有显著差异(P<0.01),此后逐渐减少,并明显低于对照组(P<0.01),缺血16周时表达最少。结论VD大鼠学习记忆的改变与海马NR2B的变化相关,缺血早期NR2B过表达产生神经毒引起该能力下降;而在慢性缺血期,这种损害则是因NR2B含量不足难以完成生理功能所致。

Objective To study the mechanism of alterations of NMDAR-2B subunit（NR2B） expression in hippoeampus of vascular dementia rats. Methods The vascular dementia rat model was established by permanent bilateral occlusion of the common carotid arteries. The water maze test was performed to detect the ability of learning and memory of the rats and the change of the expression of NR2B in hippocampus was investigated by immunohistoehemieal staining. Results As the isehemie time continued,the ability of learning and memory of VD rats decreased and significant （P〈0.01） difference was found since 4 weeks after operation,compared with the control （sham operated rats）. With the ischemic time prolonging,the expression of NR2B presented with a curve that firstly rised and then dropped. In detail ,the expression reached its peak in 2 weeks after operation（P〈0.01）,and fell down gradually,then reduced to the minimum in 16 weeks after operation（P〈0.01）. Conclusion The change of the expression of NR2B was related to the impairment of learning and memory of VD rats. During the early period of ischemia ,the impairment was concerned with neurotoxicity derived from the excessive expression of NR2B;however ,during the advanced stage ,the insufficient NR2B which was unable to perform its physiological function led to the defect of learning and memory.