β-淀粉样蛋白诱导海马神经元自噬通路启动及二苯乙烯苷的干预  

Expression of autophagy-associated protein induced by β-amyloid and effect of tetrahydroxy stilbene glucoside on it in hippocampus

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

机构地区：[1]兰州军区总医院神经内科,730050 [2]中南大学湘雅医院神经内科

出　　处：《中华神经科杂志》2012年第2期96-101,共6页Chinese Journal of Neurology

基　　金：甘肃省青年科技基金计划资助项目（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、自噬相关蛋白Beclin-1和LC3-Ⅱ的影响及何首乌提取物二苯乙烯苷（TSG）的干预作用.方法 选Wistar大鼠80只,随机数字表法分为对照组、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Aβ1-42造模,Y电迷宫及Moms水迷宫检测行为学变化,反转录聚合酶链反应及Western blot法检测制模后第21天海马神经元内自噬相关蛋白Beclin-1和LC3 -Ⅱ的mRNA及蛋白表达变化.结果 在模型组中,大鼠Y电迷宫躲避所需的电刺激次数增加,Morris水迷宫测试中潜伏期延长,游泳路程增加及穿越平台次数减少；Beclin-1和LC3-Ⅱ的mRNA及蛋白的表达一致,在21 d时,模型组Beclin-1蛋白（0.51±0.03）,LC3-Ⅱ蛋白（0.68 ±0.04）与对照组（0.31±0.01、0.31±0.02）比较,差异有统计学意义（t=28.2843、37.0000,均P＜0.05）；TSG干预后,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；Beclin-1和LC3-Ⅱ蛋白表达强度较模型组减弱,差异有统计学意义（t=9.8387、16.2698,均P＜0.05）.结论 海马神经元在受到Aβ刺激后,可上调自噬蛋白Beclin-1和LC3-Ⅱ因子表达,启动自噬通路；TSG可通过减轻内质网应激损害,下调Beclin-1和LC3-Ⅱ的表达来抵抗Aβ的神经毒性,改善大鼠行为学表现,发挥脑保护作用.Objective To observe the effect of tetrahydroxy stilbene glucoside （TSG） on the behavior on rat model and the expressions of autophagy-associated protein Beclin-1 and LC3- Ⅱ induced by Aβ1-42 Methods Eighty rats were equally randomized into 4 groups （n =20）：The control group,the sham operated group,the model group and the TSG group.The behavior of rats was measured by using Y-maze and Morris water maze.The expression of Beclin-1 and LC3- Ⅱ in rats hippocampus was detected by Western blot and RT-PCR at the time points.Results The number of electric-stimulus in hippocampus significantly increased and the Morris water maze test showed that the escape latency prolonged,swimming distance increased and the times of crossing the exact former platform location decreased both in the model and TSG groups after 21 days compared with those in control group.The mRNAs and protein expressions of Beclin-1 （0.51 ±0.03）and LC3-Ⅱ （0.68 ± 0.04） in model group were higher than that in control group （0.31 ± 0.01,0.31 ± 0.02） at that time point （ Beclin-1：t =28.2843,P 〈 0.05 ; LC3- Ⅱ ：t =37.0000,P 〈0.05）.Compared to model group,the expression of the Beclin-1 and LC3- Ⅱ was decreased at 21 d in TSG group （Beclin-1：t =9.8387,P 〈 0.05 ; LC3- Ⅱ ：t =16.2698,P 〈 0.05 ）.Conclusions Autophagy self-regulated system is started through the increased expressions of Beclin-1 and LC3- Ⅱ after Aβ deposition in rats,so as to attenuate cerebral injury caused by Aβ neurotoxicity.Autophagy pathway is possible one of the mechanisms in Aβ neurotoxic injury. Tetrahydroxy stilbene glucoside from polygonum multiflorum has protective effect on it.

关 键 词：淀粉样Β蛋白 海马 自噬 二苯乙烯类 葡糖苷类 

分 类 号：R749.16[医药卫生—神经病学与精神病学]