艾司西酞普兰对慢性脑缺血大鼠认知功能的影响

Effects of escitalopram on the cognitive function of chronic cerebral ischemic rats

目的观察艾司西酞普兰(escitalopram,ESC)对慢性脑缺血大鼠认知功能、海马区脑源性神经营养因子(BDNF)及CA1区树突长度、分支及树突棘密度的影响。方法将SD大鼠随机分为假手术组、模型组、实验组[2VO模型+30mg/(kg·d)ESC干预],采用双侧颈总动脉永久性阻断法(2VO)建立慢性脑缺血模型,选给药满1、2、4、8周4个时间点,通过Morris水迷宫检测各组大鼠的认知功能,Western blot检测大鼠海马区BDNF的表达,高尔基染色观察神经元树突长度、分支及树突棘密度的变化。结果模型组和实验组大鼠与假手术组相比逃避潜伏期明显延长(P<0.05),实验组逃避潜伏期较模型组明显缩短(P<0.05);模型组和实验组大鼠海马CA1区大锥体细胞树突长度、分支及树突棘密度较假手术组明显减少(P<0.05),实验组海马CA1区大锥体细胞树突分支及长度、树突棘密度较模型组明显增多(P<0.05);实验组和模型组海马区BDNF含量较假手术组减少(P<0.05),实验组海马区BDNF含量较模型组增多(P<0.05)。结论艾司西酞普兰能明显延缓大鼠慢性脑缺血所致认知功能障碍的进展,其机制可能是通过促进BDNF表达从而改善学习记忆能力。

Objective To investigate the effects of escitalopram （ESC） on the cognitive function, the expression of brain-derived neurotrophic factor （BDNF） in the hippocampus, the dendritic length and arborization and dendritic spines density of chronic cerebral ischemic rats. Methods Rats were randomly divided into sham- operation group, model group （permanent occlusion of bilateral common carotid arteries, 2VO） and experimental group （treated with escitalopram at the dosage of 30 mg/kg ~ d）. Rats were selected as study objects at week 1, 2, 4 and 8 after administration in each group. Their cognitive function was evaluated by the Morris water maze, the expression of BDNF protein was measured by Western blot, and dendritic morphology was studied by Golgi staining. Results In the Morris water maze test, the escape latency obviously extended in model group and experimental group compared with that in sham-operation group （P〈0.05）, while the escape latency was shorter in experimental group than in model group （P〈0.05）. Compared with those in sham-operation group, the dendritic length and arborization and the density of dendritic spines in hippocampal CA1 significantly decreased in model group and experimental group （P〈0.05）, while they increased significantly in experimental group compared with model group （P〈0.05） by Golgi staining. Compared with sham-operation group, the expression of BDNF in the hippocampus of experimental group and model group significantly decreased （P〈0.05）, but it increased significantly in experiment group compared with model group （P〈0.05） by Western blot. Conclusion Escitalopram could significantly delay the progression of cognitive impairment induced by chronic cerebral ischemia in rats. The improvement of learning and memory may be related to the increased expression of BDNF.