天津医药

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消旋丁苯肽对血管性痴呆大鼠认知功能的影响

王义义1,许静1,杨卓2   

  1. 1. 南开大学医学院
    2. 天津南开大学医学院
  • 收稿日期:2011-06-20 修回日期:2011-09-06 出版日期:2011-10-15 发布日期:2011-10-15
  • 通讯作者: 杨卓

The effect of dl-3-n-Butylphthalide on Morris water maze and long term potentiaion in vascular dementia rats

  • Received:2011-06-20 Revised:2011-09-06 Published:2011-10-15 Online:2011-10-15

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摘要： 目的: 血管性痴呆（VD）是脑血流减少引起的脑组织损伤，因而导致进行性的记忆以及认知功能的损伤。消旋丁苯肽（dl-NBP）具有减少神经元凋亡，改善缺血脑组织微循环的作用。本文中我们观察了消旋丁苯肽对VD大鼠海马CA3-CA1区长时程增强（LTP）的影响以及大鼠在Morris水迷宫（MWM）中表现的影响，以评价消旋丁苯肽对VD大鼠认知功能的影响。方法：30只Wistar大鼠随机分为三组，对照组、血管性痴呆组（VD组）、血管性痴呆 + 消旋丁苯肽干预组（VD+ dl-NBP组）。使用双侧颈总动脉结扎结合高脂喂养的方法建立血管性痴呆大鼠模型。建模后VD + dl-NBP组大鼠给予dl-NBP灌胃,40mg/kg，每天一次。30天后进行MWM测试，而后记录大鼠海马CA3-CA1区LTP。结果：在MWM定位航行阶段VD组大鼠与对照组大鼠的逃避潜伏期具有显著性差异（P<0.01），VD + dl-NBP组与VD组比较逃避潜伏期明显缩短，具有显著性差异（P<0.01）。在空间探索阶段，三组大鼠在目标象限百分比分别为51.1±2.87%，37.03±3.5% 及54.42±3.06%。VD组与对照组比较具有显著性差异（P <0.01）， VD+ dl-NBP组与VD组比较目标象限百分比明显增加，具有统计学差异（P <0.01）。在电生理实验中，三组的LTP幅值分别为133.4±10.1%，108.4±16.9%和120.5±7.3%。对照组和VD组比较以及VD组和VD+ dl-NBP组比较均有显著性（P <0.01）。结论：消旋丁苯肽对血管性痴呆大鼠的空间学习能力具有改善的作用，其机理可能与脑海马区的长时程增强的改善相关。

关键词: 血管性痴呆, 消旋丁苯肽, 长时程增强, Morris水迷宫

Abstract: Abstract: Objective Vascular dementia (VD) is one of the most common forms of dementia with a progressive decline in memory and cognitive function. In the present study, we investigated the effect of dl-3-n-Butylphthalide (dl-NBP) on learning and memory impairment induced by chronic cerebral hypoperfusion in rats. Methods Male Wistar rats fed with high fat were orally administered 40 mg/kg dl-NBP daily for 30days after bilateral permanent occlusion of the common carotid arteries. Morris water maze (MWM）test was employed to assess spatial memory and learning. The LTP induced by high frequency stimulation (HFS) at CA3-CA1 synapses of the hippocampus was recorded for measuring the slope of field excitatory postsynaptic potential (fEPSP). Results The LTP in the CA1 region of the hippocampus was enhanced more obviously in dl-NBP treatment group than that in VD group. The average amplitude of LTP was significantly increased by 120.5± 7.3% in dl-NBP treated group and 108.4±16.9% in VD group compared to those of basal condition, respectively. There was statistical significance between the two groups (P<0.01). The MWM test revealed that there were significant differences between two groups in the acquisition phase and in the retention phase, implying a considerable improvement of spatial memory in VD+dl-NBP group compared with that of VD group. Conclusion The data suggested that dl-NBP had beneficial effect on the spatial learning and memory of VD rats, also suggested the therapeutic potential for cognitive deficits of dementia induced by chronic cerebral hypoperfusion.

Key words: dl-3-n-Butylphthalide (dl-NBP), Vascular dementia (VD), long-term potentiation(LTP), Morris water maze(MWM)