2019 年第 1 期 第 14 卷

胰高血糖素样肽1对2型糖尿病合并阿尔茨海默病大鼠学习记忆功能的影响

Effect of glucagon-like peptide-1 on learning and memory abilities in Alzheimer disease and type 2 diabetes mellitus rats

作者：张翼鸿冯琨徐明艳肖玲杨艳王亦薇于淼

英文作者：

单位：150001哈尔滨，黑龙江省医院南岗院区内分泌科

英文单位：

关键词：阿尔茨海默病；2型糖尿病；胰高血糖素样肽1；学习记忆；水迷宫实验

英文关键词：

• 摘要：

• 【摘要】目的    观察胰高血糖素样肽1(GLP-1)对2型糖尿病（T2DM）合并阿尔茨海默病(AD)大鼠学习记忆功能的影响。方法    60只SD大鼠完全随机分为正常对照组、T2DM组、AD组、T2DM+AD组，各15只。T2DM组、AD组和T2DM+AD组分别制备T2DM模型、AD模型和T2DM+AD模型，模型制备成功后皮下注射GLP-1类似物利拉鲁肽注射液300 μg/（kg·d），连用4 周；正常对照组给予等体积0.9%氯化钠注射液皮下注射4周。比较干预前后大鼠体质量、空腹血糖及Ｍorris水迷宫实验评价状况。结果    干预前，与正常对照组比较，T2DM组和T2DM+AD组空腹血糖明显高，且T2DM+AD组高于T2DM组，差异均有统计学意义（均P<0.05）；干预后，T2DM组和T2DM+AD组空腹血糖较干预前明显下降，差异均有统计学意义（均P<0.05）。干预前，与正常对照组比较，AD组和T2DM+AD组逃避潜伏期明显延长［（105±12）、（114±14）s比（53±5）s］，且T2DM+AD组长于AD组，差异均有统计学意义（均P<0.05）；干预后，AD组和T2DM+AD组逃避潜伏期［（67±7）、（69±8）s］较干预前缩短，差异均有统计学意义（均P<0.05）。干预前，与正常对照组比较，AD组和T2DM+AD组第四象限游泳路程缩短，且T2DM+AD组短于AD组，差异均有统计学意义（均P<0.05）；干预后，AD组和T2DM+AD组第四象限游泳路程较干预前延长，差异均有统计学意义（均P<0.05）。干预前，与正常对照组比较，AD组和T2DM+AD组穿越平台次数减少，且T2DM+AD组少于AD组，差异均有统计学意义（均P<0.05）；干预后，AD组和T2DM+AD组穿越平台次数较干预前增多，差异均有统计学意义（均P<0.05）。结论    GLP-1对降低T2DM鼠的血糖水平及改善AD鼠的学习记忆能力均有作用，在T2DM合并AD的治疗领域可能有较大潜力。

• 【Abstract】Objective    To observe the influence of glucagon-like peptide-1(GLP-1) on learning and memory abilities in type 2 diabetes mellitus(T2DM) and Alzheimer disease(AD) rats. Methods    Sixty SD rats were randomly prepared for normal control group, T2DM model group, AD model group and T2DM+AD model group, with 15 rats in each group. After modeling, the rats were given GLP-1 analogue liraglutide by subcutaneous injection at the dose of 300 μg/(kg·d) for 4 weeks; the normal control group was given isometric subcutaneous injection of 0.9% sodium chloride for 4 weeks. Body weight, fasting blood glucose level and results of Morris water maze test were analyzed. Results    Before intervention, fasting blood glucose of rats in the T2DM group and T2DM+AD group were significantly higher than that in the normal control group; the level of blood glucose in the T2DM+AD group was significantly higher than that in the T2DM group(all P<0.05). After intervention, fasting blood glucose in the T2DM group and T2DM+AD group were significantly lower than those before intervention(both P<0.05). Before intervention, escape latencies in the AD group and T2DM+AD group were significantly longer than that in the normal control group［(105±12),(114±14)s vs (53±5)s］; escape latencies in the T2DM+AD group was significantly longer than that in the AD group(all P<0.05). After intervention, escape latencies in the AD group and T2DM+AD group［(67±7),(69±8)s］ were significantly shorter than those before intervention(both P<0.05). Before intervention, the fourth quadrant swimming distances in the AD group and T2DM+AD group were significantly shorter than that in the normal control group; the fourth quadrant swimming distance in the T2DM+AD group was significantly shorter than that in the AD group(all P<0.05). After intervention, the fourth quadrant swimming distances in the AD group and T2DM+AD group were significantly longer than those before intervention(both P<0.05). Before intervention, the numbers of platform crossings in the AD group and T2DM+AD group were significantly less than that in the normal control group; the number in the T2DM+AD group was less than that in the AD group(all P<0.05). After intervention, the numbers of platform crossings in the AD group and T2DM+AD group were significantly more than those before intervention(P<0.05). Conclusion    GLP-1 can reduce blood glucose level of T2DM rats and improve learning and memory abilities of AD rats, it may have a great potential value in the treatment of T2DM combined with AD.