文拉法辛对血管性痴呆模型大鼠学习记忆功能的影响

Effect of venlafaxine on learning and memory in rats model with vascular demential

目的研究文拉法辛对血管性痴呆（VD）模型大鼠学习记忆功能的影响及机制。方法将Wistar大鼠随机分为假手术组、模型组和治疗组，各30只。模型组和治疗组采用改良Pulsinellis四血管阻断法建立血管性痴呆大鼠模型。造模后第3天开始假手术组及模型组予蒸馏水灌胃，治疗组予文拉法辛灌胃，剂量15mg／kg，共28d。采用单程逃避实验测试各组大鼠的主动学习记忆能力，并观察各组大鼠海马及前额叶皮质5-羟色胺（5-HT）、去甲肾上腺素（NE）含量及认脑源性神经营养因子（BDNF）含量变化。结果造模后30d与假手术组大鼠单程逃避实验完成逃避的百分比数（92．3±5．6）相比，模型组完成逃避的百分比数（50．3±6．2）明显减少（P〈0．01），模型组大鼠海马及前额叶皮质5-HT、NE含量明显下降，分别为（226±34）Pg／g和（340±40）Pg／g，（601±66）Pg／g和（657±43）Pg／g（P〈0．01），BDNF含量升高，海马和前额叶皮质中吸光度分别为（0．50±0．04）和（0．49±0．04）（P〈0．05）。与模型组相比，治疗组大鼠单程逃避实验完成逃避的百分比数明显增加至（62．2±4．6）（P〈O．05），大鼠海马及前额叶皮质5-HT、NE含量升高，分别为（264±45）Pg／g和（379±42）pg／g，（798±51）pg／g和（798±51）pg／g（P〈0．05），BDNF含量进一步升高，海马和前额叶皮质中吸光度分别为（0．58±0．04）和（0．58±0．06）（P〈0．05）。结论VD大鼠海马及前额叶皮质5-HT、NE含量减少。文拉法辛能提高VD大鼠海马及前额叶皮质5-HT、NE含量，并进一步提高脑组织BDNF含量，改善大鼠学习记忆功能。

Objective To investigate the effect of venlafaxine on learning and memory ability in rats with vascular dementia（VD）. Methods Totally 90 Wistar rats were divided into sham-operation group, model group and treatment group （n： 30 for each）. The VD rat model was established by modified pulsinellis 4-vessel occlusion （4 VO）. Rats in the sham-operation group and model group were administered with gastric perfusion of distilled water. Rats in the treatment group were administrated with gastric perfusion of Venlafaxine at 15 mg/kg per day for 4 weeks from the 2nd day after the modeling. The one-way avoidance test was performed to study the learning-memory ability of each group. The contents of norepinephrine, 5-hydroxytryptamine and BDNF in the hippocampus and cortex of rats were observed. Results Model group demonstrated a decrease in the percentage of one-way avoidance test （50.3±6.2 vs. 92.3±5.6, P〈0.01） as compared with sham-operation group, and this value was increased in treatment group （62 2±4.6）. Compared with the sham-operation group, the contents of NE and 5-HT in the hippocampus [（226±34） pg/g and （340±40） pg/g], and cortex [（601± 66） pg/g and （657±43） pg/g] in rat brains of model group were decreased （P〈0.01）, while increased in treatment group [（264±45） pg/g and （379±42）pg/g, （665±68） pg/g and （798±51） pg/g, P〈0.05]. The OD value of BDNF in the hippocampus （0. 495±0. 041） and cortex （0. 488±0. 042） were increased （P〈0.05） in model group, and in treatment group, BDNF levels were more higher （0. 579±0. 044 and 0. 578±0. 064, P〈0.05）. Conclusions The content of brain monoamine neurotransmitters are decreased in rats with VD, while venlafaxine can improve the learning memory ability in model rats through increasing the levels of 5-HT, NE and BDNF in hippocampus and cortex.