首都医科大学学报 ›› 2008, Vol. 29 ›› Issue (2): 162-166.

• 基础研究 • 上一篇    下一篇

APP5肽类似物P165对2型糖尿病大鼠学习记忆的影响

邵志敏1, 张炙萍1, 赵志炜1, 庄晓明2, 姬志娟1, 张景燕1, 盛树力1, 王蓉1   

  1. 1. 首都医科大学宣武医院中心实验室, 教育部神经变性病学重点实验室;2. 首都医科大学附属复兴医院内分泌科
  • 收稿日期:2007-09-26 修回日期:1900-01-01 出版日期:2008-04-24 发布日期:2008-04-24
  • 通讯作者: 王蓉

Effect of Analog of APP 5-mer Peptide P165 on Learning and Memory Abilities in Rats with Type 2 Diabetes Mellitus

Shao Zhimin1, Zhang Zhiping1, Zhao Zhiwei1, Zhuang Xiaoming2, Ji Zhijuan1, Zhang Jingyan1, Sheng Shuli1, Wang Rong1   

  1. 1. Experiment Center, Key Laboratory for Neurodegenerative Diseases of Ministry of Education, Xuanwu Hospital, Capital Medical University;2. Department of Endocrinology, Beijing Fuxing Hospital, Capital Medical University
  • Received:2007-09-26 Revised:1900-01-01 Online:2008-04-24 Published:2008-04-24

摘要: 目的 研究APP5肽类似物P165(简称P165) 对2型糖尿病大鼠学习记忆的影响.方法 将Sprague Dawley(SD)大鼠分为正常组(C)、糖尿病组(DM)、DM+P165小剂量组、DM+P165大剂量组.采用高脂高糖饮食及腹腔注射小剂量链脲菌素(streptozotocin,STZ)的方法,建立2型糖尿病模型.成模后给予SD大鼠P165灌胃治疗8周后行水迷宫实验.每周检测动物的空腹血糖和体质量.结果 与C组相比,DM组从第2天开始逃避潜伏期明显延长(P<0.01);与DM组比较,P165治疗组逃避潜伏期明显缩短(P<0.05).空间探索实验结果显示,与C组比较,DM组第1次穿越平台所在位置时间显著延长(P<0.05),在平台所在象限游泳距离显著缩短(P<0.01);与DM组相比,P165治疗组第1次穿越平台所在位置时间明显缩短(P<0.01和P<0.05),DM+P165小剂量组在平台所在象限游泳距离显著延长(P<0.01).从给予P165治疗开始到实验结束,DM组、DM+P165小剂量组和DM+P165大剂量组动物血糖差异均无统计学意义.结论 2型糖尿病大鼠存在学习记忆功能障碍,P165能够缩短动物水迷宫实验逃避潜伏期和找到平台时间,改善模型动物的学习记忆功能,但并不影响血糖.

关键词: APP5肽类似物P165, 2型糖尿病, 水迷宫, 学习记忆, 模型, 大鼠

Abstract: Objective To investigate the effect of Analog of APP 5-mer peptide P165 on learning and memory abilities in rats with type 2 diabetes mellitus(T2 DM). Methods A total of 34 male Sprague Dawley(SD) rats were randomly divided into 4 groups: control group(C), diabetes mellitus group(DM), DM with low dose P165 group(DM+ low dose P165), DM with large dose P165 group(DM+ large dose P165). DM models were induced by high-fat and sugar diet and intraperitoneal injection of STZ(35 mg/kg). The P165 was fed through a gastric tube every day; whereas the C and DM groups were given 0.9% normal saline. Eight weeks after administration, Morris water maze was used to perform training trial and probe trial in order to detect spatial learning and memory abilities. The body weight and serum glucose were measured every week. Results After 8 weeks, the escape latency increased significantly in the DM group(P<0.01) than in the group C; in the DM+ low dose P165 and DM+ large dose P165 groups, it decreased significantly than in the DM group(P<0.05). In the Spatial probe experiment, the first time passing hidden platform prolonged significantly(P<0.05) and the distance of swimming in the quadrant of hidden platform decreased significantly in the DM group than in group C(P<0.01). But the first time passing hidden platform decreased significantly in the DM+ low dose P165 and DM+ large dose P165 than in the DM group. The serum glucose level showed no significant difference in the 3 T2 DM groups in the period of experiment. Conclusion The learning and memory abilities have been impaired in T2 DM rats. The escape latency and the first time passing hidden platform can be prolonged significantly in T2 DM rats. P165 can ameliorate the learning and memory abilities in T2 DM rats but not influence the serum glucose level.

Key words: analog of APP 5-mer peptide P165, type 2 diabetes, morris water maze, learning and memory, model, rat

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