APP17肽对APP转基因小鼠Aβ相关蛋白表达的影响  

Effect of APP17 peptide on the expression of β-amyloid associated protein in amyloid precursor protein transgenic mice

作　　者：闵嵘[1] 盛树力[1] 赵志炜[1] 姬志娟[1] 刘梦霞[1] 王蓉[1] 

机构地区：[1]首都医科大学宣武医院神经生化室,教育部神经变性病学重点实验室,北京100053

出　　处：《中国老年学杂志》2008年第12期1045-1048,共4页Chinese Journal of Gerontology

基　　金：973项目"血瘀症的生物学基础"基金重点资助(2003CB517104)

摘　　要：目的研究淀粉样前体蛋白(APP)17肽对APP转基因小鼠(APPV717I)海马神经元β淀粉样肽(Aβ)相关蛋白表达的影响。方法将3月龄的APP转基因小鼠随机分为模型组和APP17肽治疗组(隔日皮下注射0.16mg·kg-1,3次/w),并以相同年龄未经转基因处理的C57BL/6J小鼠做正常对照组。8个月后行Morris水迷宫测定,小鼠脑组织灌注固定后进行Aβ1～42、Aβ1～16、APP-N端(52～80)、早老蛋白-1(PS-1)C端、APP的β位点剪切酶(BACE)等蛋白的免疫组化染色。结果模型组小鼠水迷宫实验的逃避潜伏期明显长于APP17肽治疗组和正常对照组(P<0·05),且模型组小鼠海马中Aβ1～42、Aβ1～16、APP-N端(52～80)、PS-1C端、BACE阳性反应神经元明显增加,染色深(P<0·05);APP17肽治疗组与正常对照组相近。结论APP转基因小鼠大脑中存在Aβ相关蛋白的高表达,由此引起记忆、学习能力的改变;而APP17肽能通过抑制β-分泌酶和PS-1的表达而减少Aβ生成,使之接近正常,并能改善小鼠的记忆、学习能力。Objective To investigate the effect of amyloid protein precursor（APP） -17 peptide on the expression of β-amyloid（Aβ） associated protein in neurons of hippocampus of APP V717I transgenic mice. Methods The transgenic mice were randomly divided into model group and APP17 peptide treatment group. The mice of treatment group were injected APP17 peptide 0. 16 mg · kg^-1 every two days and three times each week. The same age and background C57BL/6J mice were selected as normal control group. Eight months later, water maze testing of behavior was conducted; then Aβ1-42, Aβ1-16, APP-N fragments（ 52 - 80） , PS-1 C fragments and BACE were measured by immunohistochemistry assay. Results Full-course swimming time of model group was obviously longer than those of APP17 treatment group and control group, and APP17 treatment group was similar to normal control group. In model group, the expression of Aβ1-42, Aβ1- 16, APP- N fragments（52 - 80）, PS-1C fragments and BACE of model group were higher than those of APP17 treatment group and control group, and APP17 treatment group was similar to normal control group. Conclusions There are high Aβ levels in the brain of APP transgenic mice. APP17 peptide can reduce the levels of Aβ by restraining the expression of BACE and PS-1 and improve learning ability and memory.

关 键 词：APP17肽 转基因小鼠 AΒ Β-分泌酶 PS-1 

分 类 号：R332.8[医药卫生—人体生理学]