文拉法辛对卒中后抑郁大鼠学习记忆及海马脑源性神经营养因子的影响

Effect of venlafaxine on cognitive function and hippocampal brain-derived neurotrophic factor expression in rats with post-stroke depression

目的:观察盐酸文拉法辛对卒中后抑郁(post-stroke depression,PSD)大鼠学习记忆障碍的改善作用,探讨盐酸文拉法辛对认知的改善与海马CA3区脑源性神经营养因子(brain-derivedneurotrophic factor,BDNF)表达变化的关系。方法:50只成年雄性SD大鼠随机分为对照组、模型组及3个文拉法辛治疗剂量组(5、10、20 mg.kg-1),每组10只。采用选择性右侧大脑中动脉栓塞后给予连续3周的慢性不可预见性温和应激方法建立卒中后抑郁大鼠模型,在慢性应激处理的同时,不同剂量的文拉法辛每日1次在固定的时间段注射入PSD大鼠腹腔。用Morris水迷宫试验评价大鼠空间学习与记忆功能,用免疫组织化学方法分析海马CA3区BDNF的表达。结果:与对照组比较,模型组大鼠学习能力显著下降(P<0.05),反映记忆功能的空间探索时间和跨平台次数均显著低于对照组,分别为(14.2±4.8)s vs(45.9±4.5)s及(1.3±0.3)次vs(8.3±1.1)次;而且BDNF阳性细胞数也较对照组下降(9.8±3.2 vs 18.5±4.7),差异具有统计学意义(P<0.05)。PSD大鼠经文拉法辛5、10及20 mg.kg-1.d-1治疗后,认知功能和BDNF表达均显著提高。结论:文拉法辛能改善卒中后抑郁大鼠学习记忆障碍;这可能与增加海马脑源性神经营养因子有关。

Objective: To evaluate the effect of venlafaxine on the cognitive impairment of learning and memory in rats with post-stroke depression(PSD) and to investigate its relationship with the expression of brain-derived neurotrophic factor(BDNF) in hippocampus. Methods: Fifty male adult SD rats were randomly divided into control group,model group and three treatment groups(5,10,20 mg·kg-1 venlafaxine) with ten in each group.After the procedure of selective cerebral right middle artery embolism,a paradigm of continuous 3-week chronic unpredictable mild stress(CUMS) was used to induce PSD.Along with the course of CUMS the peritoneal injection at different dose levels of venlafaxine were performed once a day in PSD rats in a fixed time interval.Morris water maze test was applied to assess the spatial learning and memory function and immunohistochemical staining was used to detect the change of BDNF expression. Results: The learning function decreased significantly in PSD rats compared with the control(P<0.05),as well as in spatial exploring time(14.2 s±4.8 s vs 45.9 s±4.5 s) and frequency of spanning platform(1.3±0.3 vs 8.3±1.1).Moreover,very fewer BDNF positive cells were found in CA3 area of hippocampus in model group in comparison with the control group(9.8±3.2 vs 18.5±4.7).After different dosage of venlafaxine treatment,the BDNF expression and cognition increased markedly. Conclusion: Venlafaxine can improve PSD-induced learning and memory dysfunction,possibly through the enhancement of the BDNF level in the CA3 area of hippocampus.