淀粉样蛋白诱导内质网应激的发生及二苯乙烯苷的干预影响  

Intervention effect of tetrahydroxy stilbene glucoside on amyloid protein-induced endoplasmic reticulum stress

作　　者：罗红波[1] 石向群[1] 杨金升[1] 郭建魁[2] 李芸[1] 张志强[1] 尹榕[1] 

机构地区：[1]兰州军区兰州总医院神经内科,730050 [2]兰州军区兰州总医院科训科,730050

出　　处：《中华老年心脑血管病杂志》2012年第3期315-318,共4页Chinese Journal of Geriatric Heart,Brain and Vessel Diseases

基　　金：甘肃省青年科技基金计划(1107RJYA059)

摘　　要：目的探讨在阿尔茨海默病(AD)脑损伤中,β淀粉样蛋白(Aβ)神经毒性对大鼠行为学和内质网应激分子伴侣GRP78的影响,及何首乌提取物二苯乙烯苷(TSG)的干预作用。方法选择Wistar大鼠80只,随机分为对照组、假手术组、模型组、TSG组,各20只。采用立体定向仪下于海马部位注射微量Aβ_(1 42)造模,Y电迷宫及Morris水迷宫检测行为学变化,RT-PCR及Western boh法检测制模前3 d及制模后3、21 d的海马神经元内质网分子伴侣GRP78 mRNA及蛋白的表达。结果与对照租和假手术组比较,模型组大鼠躲避电刺激次数增加,潜伏期延长,游泳路程增加及穿越平台次数减少;GRP78 mRNA及蛋白的表达一致,蛋白表达在3 d开始升高,21 d下降至正常,各时间点比较差异有统计学意义(F=182.0,P<0.05);与模型组比较,TSG组大鼠躲避所需的电刺激次数减少,潜伏期缩短,游泳路程缩短,穿越平台次数增加;GRP78表达在3 d时明显升高,差异有统计学意义(t=1 6.4317,P<0.05)。结论 Aβ可诱导内质网应激分子伴侣GRP78表达升高,启动内质网自稳调节系统;TSG可通过上调GRP78表达,抵抗Aβ的神经毒性,改善大鼠行为学表现。Objective To study the intervention effect of Aβ and tetrahydroxy stilbene glucoside （TSG） on behaviors and glucose-regulated protein 78（GRP78） in rats with AD. Methods Eighty Wistar rats were randomly divided into control group, sham operation group, model group and TSG group（20 in each group）. A model was established by injecting Aβ1-42 into the hippocampus of rats using a stereotaxic device. Changes in rat behaviors were observed by Y maze and Morris water maze tests. Expression of GRP78 mRNA and protein in hippocampus was detected by Western blot and RT-PCR,respectively, 3 days before and 3 and 21 days after the model was established. Results The number of escaped electric stimuli was greater, the latent period and the swimming distance were longer, and the number of crossing platform times was less in model group than in control group and sham operation group（P〈0.05）. The expression level of GRP78 protein began to increase on day 3 and decreased to normal on day 21（P〈0.05）. The number of escaped electric stimuli was less,the latent period and swimming distance were shorter,the number of crossing platform times was greater,and the expression level of GRP78 on day 3 was higher in TSG group than in model group and control group（P〈0. 05）. Conclusion Aβ can up-regulate the expression of GRP78 and switch on the endoplasmic reticulum self-regulated system. TSG can resist the neurotoxicity of Aβ by up-regulating its expression,thus improving the behaviors of rats.

关 键 词：阿尔茨海默病 淀粉样Β蛋白 内质网 RNA 信使 

分 类 号：R749.16[医药卫生—神经病学与精神病学]