度拉糖肽对AD小鼠学习记忆减退和突触退行性变的保护作用  

Protective Effects of Dulaglutide on the Impairment of Learning and Memory and Neurodegeneration of AD Mice

作　　者：姜国晶 周梅 俞婧 杨敏 刘筱涵 赵纲 邓艳秋 JIANG Guojing;ZHOU Mei;YU Jing(Department of Geriatrics,the Second Hospital of Tianjin Medical University,Tianjin City 300211)

机构地区：[1]天津医科大学第二医院老年病科,天津市300211 [2]天津医科大学基础医学院生理学与病理生理学系 [3]天津肿瘤医院病理科

出　　处：《医学理论与实践》2021年第14期2365-2368,共4页The Journal of Medical Theory and Practice

基　　金：国家自然科学基金(No.81270422);天津市教委科研计划项目(No.2020KJ197)。

摘　　要：目的:观察度拉糖肽对散发型阿尔茨海默病(Alzheimer’s Disease, AD)模型小鼠学习记忆、神经退行性变的影响,探讨其作用机制。方法:选取9周龄雄性野生型C57/BL6小鼠,采用随机数字表法分为对照组(CON组)、模型组(STZ组)、度拉糖肽治疗组(Dul组)和度拉糖肽加抑制剂组(Ex组),STZ、Dul和Ex组小鼠双侧脑室注射STZ(3mg/kg)建立散发型AD模型,CON组给予等量的生理盐水脑室注射。21d后,Dul组小鼠每周腹腔注射度拉糖肽,Ex组小鼠每周注射度拉糖肽和Ex9-39,CON组和STZ组给予等量无菌生理盐水,持续4周。采用Morris水迷宫系统检测小鼠的学习记忆能力,免疫印迹分析检测脑组织神经突触蛋白、cAMP反应元件结合蛋白(CREB)和Aβ表达,尼氏染色和高尔基染色检测脑组织的神经细胞和突起。结果:与STZ组和Ex组相比,Dul组小鼠的空间学习和记忆能力明显改善,脑组织内突触相关蛋白、CREB磷酸化的表达明显增加,Aβ42表达水平下降,尼氏小体及突起的数量和长度明显增加,差异有统计学意义;Ex组的结果与STZ组相比,差异无统计学意义;CON组的结果均优于其余三组,差异有统计学意义。结论:度拉糖肽对散发型AD模型小鼠学习记忆和突触退行性变有明显保护作用。Objective:Dulaglutide,a long-acting glucagon-like peptide 1 receptor(GLP-1R)agonist,has a protective effect on AD-like learning and memory impairment.In this study,we further investigated dulaglutide on learning,memory and synaptic degeneration in sporadic AD model mice and its mechanism.Methods:9-week-old male wild-type C57/BL6 mice were randomly divided into control group(CON),model group(STZ),dulaglutide treatment group(Dul)and dulaglutide plus inhibitor group(Ex).The sporadic AD model was established by bilateral intraventricular injection of STZ(3mg/kg)in groups of STZ,Dul and Ex.In the CON group,the same amount of saline was injected into the ventricle.After 21 days,mice in the Dul group were intraperitoneally injected with dulaglutide weekly,and mice in the EX group were injected with dulaglutide and Ex9-39 weekly,and mice in the CON group and STZ group were given the same amount of saline weekly.The treatment lasts for 4 weeks.Morris water maze system was used to detect the learning and memory ability of mice.The expressions of synaptic protein,cAMP-response element binding protein(CREB)and Aβin brain tissues were detected by Western blot.Nissel and Golgi staining were used to detect nerve cells and processes in brain tissues.Results:Compared with the STZ group and Ex group,the spatial learning and memory ability of mice in the Dul group were significantly improved,the expression of synapse-related protein and CREB phosphorylation in brain tissue were significantly increased with decreased expression of Aβ42,the number and length of Nissel bodies and processes were significantly increased,the difference was statistically significant.The results in the Ex group compared with that in the STZ group,the difference was not statistically significant.The results of CON group were better than the other three groups,the difference was statistically significant.Conclusion:Dulaglutide has obvious protective effects on learning and memory and synaptic neurodegeneration in sporadic AD model mice.

关 键 词：度拉糖肽 胰高血糖素样肽1 学习记忆 突触退行性变 阿尔茨海默病 

分 类 号：R-33[医药卫生]