丙戊酸钠对慢性酒中毒模型大鼠学习记忆损害的影响  

The effect of valproate on chronic ethanol exposure-induced learning and memory impairment in rats

作　　者：王岚[1] 王学义[1] 史少霞[1] 

机构地区：[1]河北医科大学第一医院精神卫生研究所河北省脑老化与认知科学重点实验室,石家庄050031

出　　处：《中国神经精神疾病杂志》2010年第5期257-260,共4页Chinese Journal of Nervous and Mental Diseases

基　　金：河北省卫生厅医学科学研究重点课题资助项目(编号:06024)

摘　　要：目的探讨慢性酒中毒对大鼠学习记忆的影响及丙戊酸钠(VPA)的干预效应及其可能机制。方法将56只SD大鼠随机分为酒中毒模型组、VPA干预组、VPA对照组和正常对照组。以乙醇浓度梯度递增式的方式灌胃8周制作慢性酒中毒模型,而第5周始酒中毒模型组腹腔注射生理盐水,VPA干预组于第5～8周腹腔注射VPA,VPA对照组灌注等体积的生理盐水4周后第5～8周给予VPA。8周后每组随机选取7只采用Morris水迷宫和Y迷宫检测大鼠的学习记忆功能,其余7只用Westernblot检测海马脑源性神经营养因子(BDNF)蛋白的表达含量。结果与正常对照组相比,酒中毒模型组大鼠水迷宫的逃避潜伏期显著延长(P<0.05),空间探索次数显著减少(P<0.05);Y迷宫中2d的错误次数显著增加(P<0.01);海马BDNF含量下降(P<0.05)。与酒中毒模型组相比,VPA干预组大鼠的行为学成绩均得到改善(P<0.01),海马BDNF含量显著增加(P<0.01),与正常对照组的差异无统计学意义(P>0.05)。VPA对照组与正常对照组各项指标的差异均无统计学意义(P>0.05)。结论慢性酒中毒可以导致大鼠学习记忆障碍,而VPA对酒精诱导的学习记忆损害有干预作用,海马BDNF表达增加可能是其作用机制之一。Objective To investigate the effect of valproate（VPA）on chronic ethanol exposure-induced learning and memory impairment in rats.Methods Fifity-six sprague-dawley（SD）rats were randomly divided into four groups：ethanol,valproate-treat,valproate-control and normal control groups.The rats were subjected to intragastric administration 8 weeks with progressively increased concentration of ethanol to create the model of chronic alcoholism.The rats were intraperitoneally injected VPA（200 mg/kg）in valproate group,but saline in ethanol and valproate control groups from the 5th week to 8th week.The Morris water maze and Y maze were used to assess learning and memory abilities and the western blot was used to detect the brain-derived neurotrophic factor（BDNF）protein in hippocampus.Results Morris water maze test demonstrated that the escape latency of chronic ethanol exposure group was remarkablly longer（P0.05）and the number of space probe was less than that of control group（P0.05）.Y maze test showed that the error number of chronic ethanol exposure group significantly increased（P0.01）.Western blot revealed a reduction of the average optical density value ratio of BDNF in hippocampus in ethanol group（P0.05）.Compared to chronic ethanol exposure group,the behavioral performances of valproate treat group and valproate control group improved（P0.01）,and BDNF in hippocampus obviously increased（P0.01）.There were no differences among the valprote control group,valprote treat group and normal control group in behavioral performances and the level of hippocampal BDNF（P0.05）.Conclusions Chronic ethanol exposure can induce the learning and memory disability.Valproate may improve ethanol-learning and memory disorder by increasing the BDNF in rat hippocampus.

关 键 词：丙戊酸钠 SD大鼠 慢性酒中毒 学习记忆 

分 类 号：R595.6[医药卫生—内科学]