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);2 Morris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。
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.
出处
《中国应用生理学杂志》
CAS
CSCD
2016年第6期567-570,共4页
Chinese Journal of Applied Physiology
