目的:观察盐酸美金刚对血管性痴呆(vascular dementia ,VaD)大鼠学习记忆能力及对N‐甲基‐D天冬氨酸受体3个亚基(NR1、NR2A、NR2B)的影响。方法将30只成年雄性SD大鼠随机分为假手术组、模型组和美金刚组,每组10只,后2组采用永久性结扎双侧颈总动脉方法制作V aD大鼠模型。美金刚组于术后1周给予美金刚10 mg/(kg · d)灌胃治疗4周,模型组给予等量生理盐水。于术后5周采用Morris水迷宫测试各组大鼠的学习记忆水平,用Western blot方法测定各组大鼠海马区NR1、NR2A和NR2B蛋白的表达水平。结果与假手术组比较,模型组大鼠术后水迷宫实验逃避潜伏期显著延长( P=0.001),跨越目标象限百分率明显减少( P=0.002),海马区NR1、NR2A、NR2B蛋白表达水平明显下降( P< 0.05)。与模型组比较,美金刚组学习记忆水平明显改善( P<0.05);NR1、NR2A、NR2B蛋白的表达显著增加(P<0.05),但仍低于假手术组(P<0.05)。结论美金刚对VaD大鼠海马区NR1、NR2A和NR2B蛋白表达均具有上调作用,从而改善其学习记忆能力。
Objective To observe the effect of memantine on NR1 ,NR2A ,NR2B of N‐methyl‐das‐partate receptor and learning or memory ability in vascular dementia (VaD) rats .Methods Thirty adult male SD rats were randomly divided into sham operation group ,VaD model group and me‐mantine treatment group (10 in each group) .A rat VaD model was established by permanent liga‐tion of bilateral common carotid arteries .Rats in memantine treatment group received gastric me‐mantine 10 mg/(kg · d) 1 week after operation while those in model group received normal sa‐line .Five weeks after operation ,their learning or memory ability was tested by Morris water maze test ,expressions of NR1 ,NR2A and NR2B were detected by Western blot .Results The escape latency was significantly longer whereas the percentage of target quadrant and expression levels of NR1 ,NR2A and NR2B were significantly lower in model group than in sham operation group (P=0 .001 ,P=0 .002 ,P〈0 .05) .The learning or memory ability and the expression levels of NR1 ,NR2A and NR2B were significantly higher in memantine treatment group than in model group but still lower in memantine treatment group than in sham operation group ( P〈 0 .05) . Conclusion Memantine can improve the learning or memory ability of VaD rats by upregulating the expression of NR1 ,NR2A and NR2B in their hippocampus .