二甲双胍改善高脂饮食诱导的大鼠学习记忆障碍

Metformin attenuates behavioral impairment in a rat model of dementia induced by high fat diet

目的探讨二甲双胍(metformin,MET)对高脂饮食诱导的大鼠学习记忆障碍的影响。方法 30只SD大鼠,随机分为普通饲料饲养组(Control组)和2个高脂饲料饲养组(high fat diet,HFD),共4周,后2组中又分为仅用HFD组及HFD+MET组。MET浓度为2 mg/ml,连续给药4周后尾尖取血检测大鼠空腹血糖及糖耐量,并测定大鼠焦虑样行为和学习记忆的变化,方法包括高架十字迷宫实验、敞箱实验、水迷宫实验、被动回避实验。结果HFD导致大鼠糖耐量降低,而MET处理可以改善大鼠糖耐量;HFD与HFD+MET处理不影响大鼠的自主活动性,也不诱导大鼠出现焦虑样症状;在水迷宫实验的探索阶段,相对于HFD组,MET+MET组大鼠穿越平台次数显著增加,第1次到达平台时间缩短,在目标象限探索时间缩短;在被动回避实验中,其逃避潜伏期较HFD组显著延长,进入暗箱次数减少。结论 MET对高脂饮食诱导的学习记忆障碍有一定的改善作用。

Objective To investigate the effect of metformin（MET） on learning and memory behavior in HFD-induced insulin-resistant rats. Methods Thirty male Sprague-Dawley （SD） rats were divided into three groups to receive either a normal diet （ Control group） or a high-fat diet （ two HFD groups） for four weeks（ HFD ＋ MET）. From two HFD groups, one received vehicle （ HFD group） alone and other MET administration （ HFD ＋ MET group）. MET was dissolved in drinking water at a concentration of 2 mg/ml. All rats were subjected to the glucose tolerance test （GTF） and behavioral tests using the elevated plus maze （ EPM ）, open field test （ OFF）, Morris water maze （ MWM ） test and the step-through passive avoidance test （PA） after four-week consecutive MET treatment. Blood samples were collected for determination of glucose. Results MET attenuated the glucose resistant condition and improved cognitive behavior in MWM and PA, vs the HFD group. Conclusion MET can improve the impaired learning and memory behavior in HFD-induced insulin-resistant rats.