二甲双胍对阿尔茨海默病小鼠的神经保护作用机制研究  

Neuroprotective and mechanism of metformin in a transgenic mouse model of Alzheimer’s disease

作　　者：邓青山 邱俊[1] 陶裕川[1] 周世军[1] 易勇[1] DENG Qing-shan;QIU Jun;TAO Yu-chuan;ZHOU Shi-jun;YI Yong(Neurosurgery Department,The Second People's Hospital of Yibing,Yibing 644000,Sichuan Province,China)

机构地区：[1]宜宾市第二人民医院神经外科,四川宜宾644000

出　　处：《中国临床药理学杂志》2022年第1期40-43,共4页The Chinese Journal of Clinical Pharmacology

基　　金：四川省医学会医学科研课题立项基金资助项目(S17080)。

摘　　要：目的研究二甲双胍处理对淀粉样蛋白前体蛋白/早老素基因1(APP/PS1)转基因小鼠神经保护作用及机制。方法将APP/PS1转基因小鼠分成模型组和实验组,将同窝野生型小鼠作为正常组,每组16只。实验组给予二甲双胍350 mg·kg^(-1)·d^(-1),正常组和模型组给予标准饮用水,连续4个月。用水迷宫实验检测3组小鼠逃生时间,以蛋白质印迹法检测沉默信息调节因子2同源蛋白1(SIRT1)、β淀粉蛋白前体蛋白(APP)、APPβ位点剪切酶1(BACE1)、β羧基末端片段(β-CTF)和核转录因子kappa B(NF-κB),酶联免疫吸附实验检测β-淀粉样蛋白(Aβ40)和β-淀粉样蛋白42(Aβ42),脑切片荧光染色检测老年斑数量,高尔基染色检测树突棘密度。结果正常组、模型组和实验组于水迷宫实验第6天的逃生时间分别为(30.08±4.26),(54.71±6.58)和(34.56±3.27)s;这3组间树突棘密度分别为(1.68±0.17),(1.05±0.17)和(1.60±0.21)cell·μm^(-1)。模型组和实验组的BACE1蛋白相对表达量分别为1.01±0.02和0.67±0.06;这2组的NF-κB蛋白相对表达量分别为1.05±0.03和0.71±0.04;这2组的老年斑数量分别为24.86±0.55和13.21±0.38;这2组的Aβ42水平分别为(2.54±0.17)和(1.13±0.09)ng·mg^(-1)。模型组与正常组比较,上述指标的差异均有统计学意义(P<0.01,P<0.001);实验组与模型组比较,上述指标的差异均有统计学意义(P<0.01,P<0.001)。结论二甲双胍长期处理可缓解APP/PS1转基因小鼠认知障碍,这可能与增加SIRT1蛋白表达与减少BACE1产生有关。Objective To explore the neuroprotective and mechanism o metformin in the brain of Amyloid precursor protein/Presenin gene 1(APP/PS1) transgenic mice.Methods The APP/PS1 transgenic mice were randomly divided into 2 groups:model group and experimenta group;the wild-type littermate mice were used as normal group(n=16for each group).The mice in experimental group were given metformin(350 mg·kg^(-1)·d^(-1)) and the mice in normal group and model group were given distilled water for 4 months.The escape latency of mice were detected by Morris Water Maze.The protein expression of Silencing information regulator 2 homolog protein 1 (SIRT1),amyloid protein precursor (APP),APPβsite shearing enzyme 1 (BACE1),nuclear transcription factor Kappa B(NF-kB) andβcarboxyl terminal fragment(β-CTF) were detected by Western blot(gray value).The level ofβ-amyloid protein 40 (Aβ40) andβ-amyloid protein 42 (Aβ42) were detected by enzyme linked immunosorbent assay.Brain sections were subjected to immunofluorescence and Gogli staining for detecting the number of plaques and spines.Results The escape latency in normal group,model group and experimental group were(30.08±4.26),(54.71±6.58),(34.56±3.27) s at 6th day,respectively;the density of Spines in normal group,model group and experimental group were (1.68±0.17),(1.05±0.17) and (1.60±0.21) cell·μm^(-1),respectively.The protein expression of BACE1 in the model and experimental groups were 1.01±0.02 and0.67±0.06,respectively;the protein expression of NF-κB in the two groups were 1.05±0.03 and 0.71±0.04,respectively;the number of plaques in the two groups were 24.86±0.55 and 13.21±0.38,respectively;the protein expression of Aβ42 in the two groups were (2.54±0.17) and (1.13±0.09) ng·mg^(-1),respectively.Comparison between model group and normal group,the difference of the indicators were significant (P<0.01,P<0.001);comparison between experimental group and model group,the difference of the indicators were significant (P<0.01,P<0.001).Conclusion The chronic metform

关 键 词：阿尔茨海默病 淀粉样蛋白前体蛋白/早老素基因1转基因小鼠 二甲双胍 Β-淀粉样蛋白 认知功能 

分 类 号：R97[医药卫生—药品]