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文拉法辛对脑卒中后抑郁大鼠认知功能及海马脑源性神经营养因子表达的影响

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

作者信息

Dai Mu-hua, Li De-qiang, Han Yang

机构信息

The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.

出版信息

Zhejiang Da Xue Xue Bao Yi Xue Ban. 2011 Sep;40(5):527-34.

Abstract

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 Compared with 45.9 s ± 4.5 s) and frequency of spanning platform (1.3 ± 0.3 Compared with 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 Compared with 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.

摘要

目的

评估文拉法辛对脑卒中后抑郁(PSD)大鼠学习记忆认知障碍的影响,并探讨其与海马区脑源性神经营养因子(BDNF)表达的关系。

方法

将50只成年雄性SD大鼠随机分为对照组、模型组和三个治疗组(文拉法辛5、10、20mg·kg⁻¹),每组10只。采用选择性大脑右中动脉栓塞术,随后用连续3周的慢性不可预测轻度应激(CUMS)范式诱导PSD。在CUMS过程中,对PSD大鼠按固定时间间隔每天腹腔注射不同剂量水平的文拉法辛。应用Morris水迷宫试验评估空间学习和记忆功能,采用免疫组织化学染色检测BDNF表达的变化。

结果

与对照组相比,PSD大鼠的学习功能显著下降(P<0.05),空间探索时间(14.2s±4.8s对比45.9s±4.5s)和跨越平台频率(1.3±0.3对比8.3±1.1)也显著下降。此外,与对照组相比,模型组海马CA3区的BDNF阳性细胞明显减少(9.8±3.2对比18.5±4.7)。不同剂量文拉法辛治疗后,BDNF表达和认知功能明显增加。

结论

文拉法辛可改善PSD所致的学习记忆功能障碍,可能是通过提高海马CA3区的BDNF水平实现的。

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