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西格列汀通过降低脑内炎性因子水平改善糖尿病小鼠学习记忆能力

Improving Effect of Sitagliptin on Learning and Memory Ability of Diabetic Mice by Reducing Levels of Inflammatory Factors in Brain
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摘要 目的 探究西格列汀对2型糖尿病小鼠学习记忆能力的影响。方法 采用高糖高脂饮食联合小剂量(80 mg/kg)链脲佐菌素(STZ)复制2型糖尿病小鼠模型,分为空白组、模型组、西格列汀组。灌胃给予西格列汀药液,每隔2 w检测小鼠体质量及空腹血糖(FBG),取血后测定C肽(C-P),空腹血清胰岛素(FINS),糖化血清蛋白(GSP),总胆固醇(TC),甘油三酯(TG),低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDL-C)含量,计算胰岛素抵抗指数(HOMA-IR);并结合自主活动、Morris水迷宫、热Y迷宫法检测小鼠的活跃程度及学习记忆认知能力。取脑组织测定炎性因子肿瘤坏死因子α(TNF-α)、白介素6(IL-6)、IL-1β含量;苏木精-伊红(HE)染色观察小鼠海马神经元形态。结果 与模型组比较,给予西格列汀药物后体质量、FBG、FINS、HOMA-IR、GSP、C-P、TC、TG、LDL-C均有不同程度的下降,HDL-C含量显著升高;自主活动活动数及站立数增多,水迷宫逃避潜伏期时间缩短,热Y迷宫学习次数及错误次数显著降低(P<0.05,P<0.01);脑组织炎性因子TNF-α、IL-6、IL-1β含量显著降低(P<0.01);空白组海马CA1、齿状回(DG)区细胞排列紧密,模型组海马CA1、DG区细胞排列较松散,西格列汀组海马CA1、DG区细胞排列松散现象减轻。结论 西格列汀能有效调节T2DM小鼠的糖脂代谢,并可能通过降低小鼠脑内炎性因子水平改善T2DM小鼠的认知能力。 Objective To investigate the effect of sitagliptin on learning and memory ability of mice with type 2diabetes mellitus(DM).Methods A model of type 2 DM in mice was prepared by high-sugar and high-fat diet combined with small dose(80 mg/kg) of streptozotocin(STZ),which was divided into blank group,model group and sitagliptin group.Animals were given sitagliptin by gavage,and the body mass and fasting blood glucose(FBG)of mice were detected every 2 w,and levels of C peptide(C-P),fasting serum insulin(FINS),glycosylated serum protein(GSP),total cholesterol(TC) and triglycerides(TG),and low-density lipoprotein cholesterol(LDL-C) and high-density lipoprotein cholesterol(HDL-C) were determined.The insulin resistance index(HOMA-IR) was also calculated.Autonomous activity detection,Morris water maze test and hot Y maze test were adopted to determine the active level and learning and memory ability of mice.Brain tissues were taken to determine the levels of inflammatory factors including tumor necrosis factor-α(TNF-α),interleukin-6(IL-6) and interleukin-1β(IL-1β).The morphology of hippocampal neurons in mice was observed by hematoxylin-eosin(HE) staining.Results Compared with the model group,after administration of sitagliptin,the body weight,FBG,FINS,HOMA-IR,GSP,CP,TC,TG and LDL-C decreased to varying degrees,and the content of HDL-C significantly increased.The number of voluntary activity and standing in autonomous activity detection increased,and the escape latency time of Morris water maze test was shortened,meanwhile the number of learning times(P<0.05) and the number of errors(P<0.01) in the hot Y maze test significantly decreased.The contents of inflammatory factors including TNF-α,IL-6 and IL-1β in brain tissues significantly decreased(P<0.01).The cells in the hippocampal CA1 and dentate gyrus(DG) areas of the animals in blank group were closely arranged,while the cells in the model group were loosely arranged in the hippocampal CA1 and DG areas,and the loose arrangement of cells in hippocampal CA1 and DG re
作者 韩丽男 周游 陈旭 李佳男 HAN Li-nan;ZHOU You;CHEN Xu;LI Jia-nan(College of Pharmacy,Harbin University of Commerce,Harbin 150076,China)
出处 《食品与药品》 CAS 2023年第2期182-187,共6页 Food and Drug
关键词 2型糖尿病 西格列汀 糖脂代谢 炎性因子 认知 type 2 diabetes mellitus sitagliptin glucose and lipid metabolism inflammatory factor cognition
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