β淀粉样前体蛋白17肽对糖尿病大鼠海马神经细胞线粒体膜电位和凋亡的干预(英文)  

APP17-mer peptide in regulation of neuronal mitochondrial transmembrane potentials and apoptosis in the hippocampus of diabetic rats

作　　者：李红星[1] 王蓉[1] 杜怡峰[1] 姬志娟[1] 盛树力[1] 

机构地区：[1]首都医科大学宣武医院北京脑老化研究实验室,北京市100053

出　　处：《中国临床康复》2005年第44期179-181,F0003,共4页Chinese Journal of Clinical Rehabilitation

基　　金：国家科技部"九七三"课题资助项目(G2000057010)~~

摘　　要：背景:糖尿病大鼠存在学习和记忆障碍,β淀粉样前体蛋白17肽具有改善这一行为的作用。糖尿病是否通过影响海马区神经细胞的膜电位及凋亡导致学习和记忆障碍以及β淀粉样前体蛋白17肽的相关作用机制尚不清楚。目的:观察糖尿病大鼠海马区神经细胞的线粒体膜电位和凋亡以及β淀粉样肽前体蛋白干预对其影响。设计:完全随机分组设计,对照实验。单位:首都医科大学宣武医院北京脑老化研究实验室和河北保定市第一中心医院内分泌科。材料:实验中指标测定部分于2002-05/2002-08在解放军总医院仪器测试中心完成。动物造模及干预阶段在首都医科大学附属宣武医院动物室完成。选用Wistar雄性大鼠18只。将大鼠按随机抽签法分为3组,正常对照组,糖尿病模型组,β淀粉样前体蛋白17肽治疗组,每组6只。方法:①糖尿病模型组和β淀粉样前体蛋白17肽治疗组大鼠禁食12h后用pH值4.4链脲佐菌素按60mg/kg腹腔注射诱发糖尿病模型。3d后测尾静脉血糖>15mmol/L为造模成功。正常对照组大鼠不造模。β淀粉样前体蛋白17肽治疗组于背部皮下注射β淀粉样前体蛋白17肽,3.4μg/只,每周3次,共10周。正常对照组及糖尿病组给予等量的生理盐水相同部位注射,每周3次,共10周。②满10周时,将大鼠麻醉,断头取脑后冰浴下取海马组织制备单细胞悬液,采用线粒体膜电位特异性荧光探针JC-1标记线粒体及Annexin-V-FITC&PI双染色技术,进行流式细胞仪上机检测线粒体膜电位和凋亡发生率。③数据间差异比较采用单因素方差分析。主要观察指标:各组大鼠海马神经细胞线粒体膜电位和海马单细胞凋亡率比较结果。结果:进入结果分析大鼠18只,每组6只。①海马神经细胞线粒体膜电位:糖尿病模型组明显低于正常对照组[(551.91±53.36),(809.88±82.41)道,P<0.01],β淀粉样前体蛋白17肽治疗组高于糖尿病模型组[(705BACKGROUND： Learning and memory disorder exist in diabetic rats, which can be improved by APP 17-mer peptide. However, it is unclear whether learning and memory disorder in diabetes mellitus is caused by influencing neuronal mitochondrial transmembrane potentials and apoptosis in hippocampus or not and what is the related action mechanism of APP17-mer peptide. OBJECTIVE： To observe the effects of APP17-mer peptide on neuronal mitochondrial transmembrane potentials （△ψam） and apoptosis in hippocampal area of diabetic rats. DESIGN： A completely randomized, grouping and controlled trial. SETTING： Beijing Research Laboratory for Brain Aging, Beijing Xuanwu Hospital, Capital University of Medical Sciences; the Department of Endocrine, the First Central Hospital of Baoding. MATERIALS： The data measurement of the experiment was carried out in the Instrument Testing Center, the General Hospital of Chinese PLA between May 2002 and August 2002. The modeling and intervention of the experiment was carried out in the Animal Laboratory of Xuanwu Hospital, Capital University of Medical Sciences. Eighteen male Wistar rats were enrolled and randomized into control group, model group and APP17-mer peptide group with 6 rats in each group. METHODS： ①Diabetic models in the model and APP17-mer peptide groups were established by intraperitoneal injection of 60 mg/kg strepto- zotocin （pH=4.4） in fasted rats（fasting for 12 hours）. Three days later, modeling was successful if blood sugar level in caudal vein was more than 15 mmol/L. Rats in the control gro.up were not subjected to modeling. Then, the rats in the APP17-mer peptide group were subjected to the sub- cutaneous injection of APP17-mer peptide （3.4 μg for each rat once） three times a week and totally for ten weeks, whereas rats in the other groups were given saline of the same volume. ②After ten weeks, rats were anesthetized and decapitated to take out brain tissues, and then hippocampal tissues were isolated in ice bath for preparation of sing

关 键 词：肽类 线粒体膜电位 细胞凋亡 海马/病理学 脑疾病/病理学 线粒体 膜电位 

分 类 号：R587.1[医药卫生—内分泌]