APP/PS1双转基因AD小鼠早期内质网应激诱导的凋亡  

The early endoplasmic reticulum stress-induced apoptosis in the amyloid precursor protein(APP)/presenilin-1(PS1) transgenic Alzheimer disease mouse model

作　　者：陈静[1] 秦红芳[1] 朱斌[1] 邓汝东[1] 李伊为[1] 黎晖[1] 周健洪[1] 张赛霞[1] 宋述财[1] 陈云波[2] 魏刚[3] 陈东风[1] 

机构地区：[1]广州中医药大学人体解剖学教研室,广东广州510405 [2]广州中医药大学临床药理研究所,广州510405 [3]广州中医药大学新药开发研究中心,广州510006

出　　处：《解剖学研究》2012年第1期12-15,共4页Anatomy Research

基　　金：国家科技重大专项(重大新药创制)项目(2009ZX09103-429)

摘　　要：目的观察APP/PS1双转基因AD小鼠神经细胞凋亡,及内质网分子伴侣葡萄糖调节蛋白(GRP78)和内质网促凋亡因子半胱氨酸蛋白酶-12(Caspase-12)表达的改变,探讨APP/PS1双转基因AD小鼠早期内质网应激诱导的凋亡。方法选取5、7月龄的APP/PS1双转基因小鼠和同月龄同背景的野生型小鼠(WT),分为5月龄WT组、5月龄APP/PS1组、7月龄WT组和7月龄APP/PS1组,每组6只,应用原位细胞凋亡检测法(TUNEL)检测凋亡细胞,免疫组织化学方法检测其脑内GRP78和Caspase-12的表达水平。结果 TUNEL检测凋亡率分别为7月龄APP/PS1鼠(35.0±6.31)%、5月龄APP/PS1鼠(9.0±2.78)%、7月龄WT鼠(4.0±1.89)%、5月龄WT鼠(4.0±1.83)%,其中7月龄APP/PS1鼠凋亡率显著升高(P<0.05);免疫组织化学检测GRP78阳性率分别为7月龄APP/PS1鼠(30.0±5.43)%、5月龄APP/PS1鼠(10.0±2.12)%、7月龄WT鼠(2.0±1.71)%、5月龄WT鼠(3.0±1.41)%,7月龄APP/PS1鼠GRP78表达明显升高(P<0.05);免疫组织化学检测Caspase-12阳性率分别为7月龄APP/PS1鼠(33.0±5.98)%、5月龄APP/PS1鼠(12.0±2.60)%、7月龄WT鼠(4.0±2.56)%、5月龄WT鼠(2.0±1.79)%,7月龄APP/PS1鼠Caspase-12表达明显升高(P<0.05)。结论 7月龄的APP/PS1双转基因小鼠出现了内质网应激诱导的凋亡。本实验结果为临床AD早期预防和治疗提供了重要依据。Objective To investigate the early endoplasmic reticulum stress-induced apoptosis of the amyloid precursor protein（APP）/presenilin-1（PS1） double transgenic Alzheimer disease（AD） mouse model.Methods Mice which divided into 5-month-old WT group,5-month-old APP/PS1 group,7-month-old WT group and 7-month-old APP/PS1 groups of six,were studied the expression of GRP78 and Caspase-12 by immunohistochemistry.Apoptosis was evaluated by means of terminal deoxynucleotidyl transferase-mediated d-UDP nick-end labeling（TUNEL） method.Results（1）The rates of apoptosis detected with TUNEL was（35.0±6.31）% of 7-month APP/PS1 mice,（9.0±2.78）% of 5-month APP/PS1 mice,（4.0±1.89）% of 7-month WT mice,（4.0±1.83）% of 5-month WT mice respectively,and the rate of apoptosis in 7-month APP/PS1 mice was significantly increased compared to 5-month-old APP/PS1 transgenic mice and wildlife mice（P0.05）.（2）The positive cells of GRP78 tested with immunohistochemistry were（30.0±5.43）% of 7-month APP/PS1 mice,（10.0±2.12）% of 5-month APP/PS1 mice,（2.0±1.71）% of 7-month WT mice,（3.0±1.41）% of 5-month WT mice respectively,the expression of GRP78 in 7-month APP/PS1 mice was increased significantly compared to 5-month-old APP/PS1 transgenic mice and wildlife mice（P0.05）;the positive cells of Caspase-12 were（33.0±5.98）% of 7-month APP/PS1 mice,（12.0±2.60）% of 5-month APP/PS1 mice,（4.0±2.56）% of 7-month WT mice,（2.0±1.79）% of 5-month WT mice respectively,and the expression of GRP78 in7-month APP/PS1 mice was increased significantly compared to 5-month-old APP/PS1 transgenic mice and wildlife mice（P0.05）.Conclusion The 7-month-old APP/PS1 transgenic mice had been already seen an obvious endoplasmic reticulum stress-induced apoptosis.Our results provided an important basis for early prevention and treatment of clinical AD.

关 键 词：阿尔茨海默病 内质网应激 APP/PS1双转基因小鼠 凋亡 

分 类 号：R749.16[医药卫生—神经病学与精神病学]