氨基胍通过减轻内质网应激改善糖尿病小鼠认知功能  

Aminoguanidine improved the cognitive function of type 2 diabetic mice by reducing ERS

作　　者：方洁[1,2] 邓雅欣 王鹏宇 陈曦[1,2] 邵德翠[1] 汪萌芽[1] FANG Jie;DENG Yaxin;WANG Pengyu;CHEN Xi;SHAO Decui;WANG Mengya(Cell Electrophysiology Laboratory,Wannan Medical College,Wuhu 241002,China)

机构地区：[1]皖南医学院细胞电生理研究室,安徽芜湖241002 [2]皖南医学院启明星小组,安徽芜湖241002

出　　处：《皖南医学院学报》2019年第5期409-413,共5页Journal of Wannan Medical College

基　　金：国家自然科学基金项目(81400695,31271155);国家级大学生创新创业训练计划项目(201610368009)

摘　　要：目的:观察氨基胍(AG)能否改善2型糖尿病(T2DM)小鼠认知功能,并探讨内质网应激(ERS)在其过程中的作用。方法:昆明小鼠随机分为对照组(Ctrl组),糖尿病组(DM组)和氨基胍组(AG组)。DM组和AG组小鼠给予高糖高脂饮食(HFD)4周后腹腔注射单剂量链脲霉素(STZ,120mg/kg,ip),继续予以HFD饮食喂养4周后,AG组小鼠用氨基胍灌胃治疗2周,其余小鼠灌入等量生理盐水。跳台实验检测小鼠行为学认知能力;HE染色观察小鼠海马神经元细胞形态的变化;Westernblot检测海马GluR1、GluR2、Bip、XBP1s的蛋白表达水平。结果:跳台实验显示,与Ctrl组相比,DM组的潜伏期缩短(P<0.01),错误次数增多(P<0.05);经氨基胍治疗后,AG组的潜伏期较DM组延长(P<0.01)且错误次数少于DM组(P=0.051)。HE染色结果显示DM组小鼠海马神经元细胞核固缩,细胞质减少,细胞排列紊乱。Westernblot结果显示DM组AMPA受体(GluR1,GluR2)表达水平较Ctrl组升高(P<0.05,P<0.01),经AG治疗后呈降低趋势。与Ctrl组相比,DM组内质网应激标记蛋白(Bip和XBP1s)表达水平升高(P<0.01),经AG治疗后下降(P<0.05,P<0.01)。结论:AG可能通过减轻ERS途径从而有助于改善早期T2DM小鼠的认知功能。Objective: To investigate whether aminoguanidine (AG) can improve the cognitive function of mice with type 2 diabetes mellitus (T2DM),and the effect of endoplasmic reticulum stress (ERS) in the modification processes. Methods :KM mice were randomized into control group,DM group and AG group.Mice in DM and AG group were fed with high fat diet (HFD) for 4 weeks,followed by single dosage of streptozotocin injection(STZ,120 mg/kg,ip) and resumed feeding with HFD for another 4 weeks.Then mice in AG group were treated with AG by gavage for 2 weeks,and the remainder were managed with equivalent saline.Step-down test was performed to test the behavioral function.Changes of neurons in hippocampus were observed by HE staining,and levels of AMPA receptors (GluR1 and GluR2) and ERS(Bip,XBP1s) in hippocampus were detected by Western blot. Results :Shorter latency and increased number of errors in step-down test were found in mice in DM group compared to the control group( P< 0.01;P< 0.05),yet increased latency and reduced number of errors were seen in mice in AG group following AG treatment as compared with DM group( P< 0.01;P= 0.051).HE staining revealed cytoplasmic reduction,pyknosis of nuclei and disorganized arrangement of cells,and Western blotting indicated increased protein levels of GluR1,GluR2 in mice in DM group compared to control group( P< 0.05, P< 0.01).These changes tended to be downward following AG treatment.Significantly increased expression of Bip and XBP1s was seen in DM group than in control group( P< 0.01),yet the expression was down-regulated after AG treatment( P< 0.05, P< 0.01). Conclusion :These results indicate that AG may improve the early T2DM cognitive impairment by reducing ERS.

关 键 词：2型糖尿病 认知障碍 AMPA受体 氨基胍 内质网应激 

分 类 号：R-332[医药卫生] R338.1