二甲双胍对小鼠衰老过程中学习记忆能力的影响

Effect of metformin on learning and memory ability in mice during aging and the possible underlying mechanisms

目的探究D-半乳糖诱导小鼠衰老过程中补充二甲双胍对小鼠学习记忆能力的影响及可能机制。方法将24只雌性ICR小鼠随机分为3组:对照组、衰老组、衰老+二甲双胍组,每组8只,连续给药16周。监测各组小鼠体重及食物摄取量;行为学检测小鼠学习记忆能力;HE染色观察小鼠海马组织结构;比色法检测各组小鼠海马组织中谷胱甘肽(glutathione,GSH)水平。结果与衰老组相比,衰老+二甲双胍组小鼠体重降低(P<0.05);Morris水迷宫逃避潜伏期、游泳路程明显减少(P<0.01或P<0.05),目标象限内游泳时间延长(P<0.05),游泳速度加快(P<0.05);穿梭实验中主动回避次数升高(P<0.05);HE染色显示海马齿状回中核皱缩、深染的海马神经元明显减少;海马组织GSH水平显著升高(P<0.05)。结论补充二甲双胍可以明显延缓小鼠衰老过程中学习记忆能力的下降,维持海马神经元正常结构,其机制可能与降低小鼠体重及增强海马组织抗氧化水平有关。

bObjective To explore the effect of metformin on learning and memory ability and hippocampal tissue structure in mice during aging induced by D-galactose,and the possible underling mechanisms. Methods Twenty-four SPF 7-month-old female ICR mice were randomly divided into three groups. Mice of the aging group and aging ＋ metformin group were given subcutaneous injection with D-galactose on the back to induce senescence,and given intragastric gavage with 0. 9% saline or metformin. Mice of the control group were treated with 0. 9% saline. All treatments lasted for 16 weeks. The body weight and food intake were monitored,learning and memory ability and motor function were tested by Mirros water maze and shuttle box tests,HE staining was used to observe the pathology of hippocampus in the mice,and the levels of glutathione（ glutathione,GSH） in hippocampus of mice were detected by colorimetry. Results Compared with the aging group,the aging ＋ meformin group showed diverse differences： the body weight was decreased（ P〈 0. 05）,the escape latency and swimming distance were decreased（ P〈 0. 01 or P〈 0. 05）,the swimming time in the targetquadrant was prolonged（ P〈 0. 05） and swimming speed was accelerated（ P〈 0. 05） in the Morris water maze test.The numbers of active avoidance response were markedly increased in shuttle box test（ P〈 0. 05）. The neurons with nuclear condensation and deep staining were obviously decreased in the dentate gyrus of hippocampus,however the GSH level was significantly increased（ P〈 0. 05）. Conclusions Metformin can delay the decline of learning and memory ability,maintain the normal structure of hippocampus during the aging process in mice,which may be related to the reduction of body weight and enhancement of antioxidant levels in the hippocampus.