西格列汀对阿尔茨海默症大鼠的学习和记忆功能的影响  

Effects of Sitagliptin on the Learning and Memory Abilities in Rats with Alzheimer s Disease

作　　者：何震杰 张浩楠 王旭 王心怡 奚培焱 宋锦辉 姜海英 He Zhenjie;Zhang Haonan;Wang Xu;Wang Xinyi;Xi Peiyan;Song Jinhui;Jiang Haiying(College of Medicine,Jiaxing University,Jiaxing,Zhejiang 314001;School of Basic Medical Science,Zhejiang Chinese Medical University,Hangzhou,Zhejiang 310000)

机构地区：[1]嘉兴大学医学院,浙江嘉兴314001 [2]浙江中医药大学基础医学院,浙江杭州310000

出　　处：《嘉兴大学学报》2024年第6期31-35,共5页Journal of Jiaxing University

基　　金：国家自然科学基金项目(81760207);浙江省大学生科技创新活动计划(新苗人才计划)项目(2023R417A017);嘉兴大学大学生科技创新训练计划项目(8517231302,8517221153)。

摘　　要：将雄性大鼠随机分为假手术组(Control组)、假手术+西格列汀组(Control+SGLT组)、阿尔茨海默症模型组(Alzheimer s disease,AD)(AD组)和AD+西格列汀组(AD+SGLT组).采用海马齿状回微量注射Aβ25-35制备AD大鼠模型,并经Morris水迷宫实验观察大鼠的学习和记忆功能,再利用蛋白免疫印迹法检测大鼠海马组织和HT22神经元细胞凋亡相关信号蛋白的表达水平.结果显示,定位航行实验中,AD组逃避潜伏期明显长于Control组,AD+SGLT组逃避潜伏期与AD组相比明显缩短;空间探索实验中,AD+SGLT组的穿台次数和目标象限停留时间百分比与AD组相比均显著增加.Western blot实验结果显示,与Control组相比,AD组Caspase-8、Caspase-3和Bax表达水平明显增强,而西格列汀显著降低AD组Caspase-8、Caspase-3和Bax表达水平,同时,显著增加Bcl-2表达水平.说明西格列汀具有抑制DPP4调控细胞凋亡通路的作用,能改善AD模型大鼠的学习和记忆功能.Male rats were randomly divided into sham operation group(Control group),sham operation+sitagliptin group(Control+SGLT group),Alzheimer’s disease model group(AD group),and AD+sitagliptin group(AD+SGLT group).The AD model was established by microinjection of Aβ25-35 into the dentate gyrus of the hippocampus.Morris water maze test was used to observe the learning and memory abilities of the rats.Western blot was used to detect the expression levels of apoptosis-related proteins in hippocampus and HT22 neurons.Results showed that in the navigation experiment,the escape latency of the AD group was significantly longer than that of the Control group,and the escape latency of the AD+SGLT group was significantly shorter than that of the AD group.In the space exploration test,the number of platform crossings and the percentage of target quadrant residence time of the AD+SGLT group were significantly increased compared with those of the AD group.Western blot results showed that the expression levels of Caspase-8,Caspase-3 and Bax in the AD group were significantly higher than those in the Control group,while sitagliptin significantly reduced the expression levels of Caspase-8,Caspase-3 and Bax in the AD group.At the same time,it significantly increased the expression level of Bcl-2.These results suggest that sitagliptin has the effect of inhibiting the DPP4 in regulating the cell apoptosis pathway and can improve AD model rats’spatial learning and memory abilities.

关 键 词：西格列汀 二肽基肽酶4 阿尔茨海默症 学习和记忆 凋亡 

分 类 号：R736[医药卫生—肿瘤]