APP17肽调节胰岛素受体底物1在糖尿病小鼠脑内分布及对脑海马区神经元退行性变的作用(英文)  

Effects of amyloid beta protein precursor 17 peptide on distribution of insulin receptor substrate-1 in brain and degeneration of neurons in hippocampus of diabetic mice

作　　者：陆珊[1] 雷亚平[1] 崔艳君[1] 王蓬文[1] 盛树力[2] 

机构地区：[1]首都医科大学基础医学院病理学教研室,北京市100069 [2]宣武医院脑老化研究室,北京市100069

出　　处：《中国临床康复》2006年第20期181-183,共3页Chinese Journal of Clinical Rehabilitation

基　　金：北京市自然科学基金重点项目(7031003)~~

摘　　要：背景:胰岛素在脑内通过胰岛素受体底物发挥作用,APP17肽有神经营养功能,可能通过影响胰岛素受体底物改善胰岛素缺乏引起的糖尿病脑病。目的:制备小鼠糖尿病模型熏观察APP17肽对糖尿病小鼠胰岛素受体底物1的影响。设计:随机对照动物实验。单位:首都医科大学基础医学院病理学教研室,宣武医院脑老化研究室。材料:实验于2003-09/10在首都医科大学基础医学院病理学教研室及宣武医院脑老化研究室完成,选择雄性昆明小鼠18只,随机分为正常对照组、糖尿病组和APP17肽治疗组3组,每组6只。方法:①糖尿病组和APP17肽治疗组小鼠按200mg/kg剂量腹腔注射链脲佐菌素熏3d后测尾部非禁食血糖熏大于15mmol/L者被认为糖尿病模型建立。②APP17肽治疗组于糖尿病造模2周后皮下注射APP17肽熏每次0.35μg/只熏1次/d熏共注射2周。正常对照组大鼠不干预。③给链脲佐菌素4周后熏处死动物取脑组织进行胰岛素受体底物1免疫组化染色。主要观察指标:各组小鼠脑胰岛素受体底物1阳性细胞形态及分布。结果:18只小鼠全部进入结果分析。①糖尿病组胰岛素受体底物1阳性反应细胞广泛分布于皮质、海马、丘脑、下丘脑等部位熏而正常对照组及APP17肽治疗组仅在皮质、海马见有阳性反应细胞熏且着色淡。②糖尿病组、正常对照组及APP17肽治疗组脑海马胰岛素受体底物1免疫组化阳性反应细胞数分别为(28.7±1.5),(9.2±1.5),(10.1±1.4)个/10倍物镜,糖尿病组高于其他两组(P<0.001)。结论:糖尿病小鼠脑内多个区域的神经元存在较多的胰岛素受体底物1阳性细胞熏APP17肽能使胰岛素受体底物1阳性反应细胞出现的部位和数量正常化熏从而改善糖尿病小鼠海马神经元的退行性变。BACKGROUND： In brain insulin does its work through the insulin receptor substrate （IRS）. Amyloid beta protein precursor 17 （APPI7） peptide has the neurotrophic function, which may improve diabetic encephalopathy resulted from insulin deficiency by affecting insulin receptor substrate. OBJECTIVE： The mouse diabetic model was produced to observe the effect of APP17 peptide on the distribution of IRS-1 in brain tissues. DESIGN： Randomized control animal experiment. SETTING： Staff Room of Pathology, College of Basic Medical Sciences, Capital University of Medical Sciences; Beijing Research, Laboratory for Brain Aging of Xuanwu Hospital. MATERIALS： The experiment was performed in Staff Room of Pathology, College of Basic Medical Sciences, Capital University of Medical Sciences and Beijing Research Laboratory for Brain Aging of Xuanwu Hospital from September to October 2003. Totally 18 male kunming mice were employed, and randomly assigned into control group, diabetic group and APP17 peptide treatment group with 6 mice in each group. METHODS： ①The mice were subjected to intraperitoneal injection of streptozotocin （STZ, Sigma） by 200 mg/kg, and 3 days later, the tail blood was sampled to examine non-fasting blood glucose, and the blood glucose over 15 mmol/L was set as the criteria for successful diabetic model establishment. ②In APP17 ＋ diabetes mellitus group, the mice received subcutaneous injection of 0.35 μg APP17 peptide once daily for 2 weeks. The mice in the normal control group were not interfered. ③Then brain was removed and crystat sections were prepared. Immunohistochemical staining was done for IRS-1 at four weeks after giving streptozotocin. MAIN OUTCOME MEASURES： Pattern and distribution of IRS-I posi- tive cells of mice in each group. RESULTS： Totally 18 mice were involved in the result analysis. ①In the brains of diabetic mice the IRS-1 immunohistochemical positive cells distfibuted at cortex, hippocampus, thalamus, hypothalamus and so on, while the p

关 键 词：糖尿病 受体 胰岛素 淀粉样Β蛋白前体 小鼠 

分 类 号：R587.1[医药卫生—内分泌]