双受体激动剂CI-1206拮抗Aβ1-42所致小鼠空间学习记忆损伤的作用

doi:10.13459/j.cnki.cjap.2016.06.018

摘要/Abstract

摘要： 目的：探讨葡萄糖依赖性促胰岛素释放激素（GIP）和胰高血糖素样肽1（GLP-1）双受体激动剂CI-1206拮抗淀粉样β蛋白（Aβ）所致小鼠空间工作记忆及长时程记忆损伤的作用。方法：C57小鼠经侧脑室注射Aβ1-42寡聚体建立AD动物模型，经腹腔注射CI-1206进行药物干预，随机分为对照组（saline + D-PBS）、Aβ1-42 + saline、CI-1206+ D-PBS、Aβ1-42 + CI-1206组（n=12），而后联合应用Y-迷宫和Morris水迷宫行为学手段检测小鼠空间学习记忆。结果：①Aβ1-42 + saline组小鼠在Y迷宫自发交替实验中进臂正确百分比明显低于对照组（P < 0. 05）；Aβ1-42 + CI-1206组则明显高于单独给予Aβ1-42组（P < 0.05）；②Morris水迷宫结果显示，与对照组相比，Aβ1-42 + saline组的小鼠逃避潜伏期明显延长，目标象限游泳时间百分比降低（P < 0. 05），经CI-1206处理可明显改善（P < 0. 05）；③Aβ1-42和CI-1206均不影响小鼠的运动能力和视力。结论：脑室注射Aβ影响小鼠短期工作记忆及长期空间学习记忆能力；腹腔注射CI-1206可拮抗Aβ1-42所致的短期和长期记忆损伤。

关键词: CI-1206, 淀粉样β蛋白, Y迷宫, Morris水迷宫, 空间学习记忆, 小鼠

Abstract: Objective: To study the neuroprotective effects of a novel GIP/GLP-1 receptor dual agonist CI-1206 against Aβ1-42-induced impairments in spatial working memory and long term memory in mice. Methods: C57 mice, after receiving intracerebralventricular (i.c.v.) injection of Aβ1-42 and intraperitoneal injection of CI-1206, were divided into the following groups:saline+D-PBS, Aβ1-42+saline, CI-1206+D-PBS and Aβ1-42+CI-1206 group (n=12). Y maze spontaneous alternation of mice was tested to assess short term working memory, and Morris water maze task was used to assess long term reference memory. Results: ①The percentage of right alternation of mice in Aβ1-42+saline group was significantly decreased, while the percentage in Aβ1-42+CI-1206 group was significantly larger than that in Aβ1-42 alone group (P<0.05). ②In Morris water maze test, the escape latency of mice in Aβ1-42+saline group showed a significant increase, with a significant decline in swimming time in target quadrant. Treatment with CI-1206 significantly antagonized these detrimental effects induced by Aβ1-42. ③Aβ1-42 and CI-1206 did not affect the motor ability and vision of mice. Conclusion: I.C.V. administration of Aβ1-42 impaired the short term and long term spatial memory of mice, while CI-1206 could effectively antagonize the detrimental effects.

Key words: CI-1206, Amyloid &beta, protein, Y-maze, Morris water maze, spatial learning and memory, mouse

中图分类号:

杨菊, 张军, 原丽, 曲雪松, 祁金顺. 双受体激动剂CI-1206拮抗Aβ1-42所致小鼠空间学习记忆损伤的作用[J]. 中国应用生理学杂志, 2016, 32(6): 567-570.

YANG Ju, ZHANG Jun, YUAN Li, QU Xue-song, QI Jin-shun. Dual co-agonist CI-1206 antagonizes Aβ1-42-induced impairments in spatial learning and memory in mice[J]. CJAP, 2016, 32(6): 567-570.

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