| 摘要: |
| 目的 观察β-细辛醚对APPswe/PS1dE9双转基因小鼠脑组织中差异蛋白表达的调节作用，探讨其对阿尔茨海默病（Alzheimer disease，AD）的治疗作用机制。方法 实验动物分为正常对照组（C57BL/6J小鼠）、模型组（APPswe/PS1dE9小鼠）和β-细辛醚治疗组（APPswe/PS1dE9小鼠），每组10只。β-细辛醚治疗组用灌胃方法给药，正常对照组和模型组给予等量生理盐水，历时90 d。用Morris水迷宫行为学方法测试小鼠学习记忆能力，用免疫组织化学方法检测小鼠脑组织中β-淀粉样前体蛋白（APP）的表达。用同位素标记相对和绝对定量（iTRAQ）技术对小鼠脑组织进行蛋白质组学分析，用蛋白质印迹法鉴定差异蛋白H2A、H2B的表达。结果 与模型组小鼠比较，经β-细辛醚治疗后，小鼠的逃避潜伏期和第1次穿越平台时间缩短（P<0.05），平台穿越次数增多（P<0.05），APP的表达减少（P<0.05），差异蛋白组蛋白H2A 1-H、H2B 2-E和H2B 1-F/J/L的表达水平下降（P<0.05）。结论 β-细辛醚能够介入到组蛋白的修饰过程而起到治疗作用，这可能是其改善β-淀粉样肽毒性所致学习记忆能力下降的机制之一。 |
| 关键词: 阿尔茨海默病 β-细辛醚 双转基因小鼠 组蛋白类 蛋白质修饰 |
| DOI：10.16781/j.0258-879x.2017.10.1286 |
| 投稿时间：2017-07-31修订日期：2017-09-12 |
| 基金项目:国家自然科学基金（30870986），贵州省科教青年英才培养工程项目[黔省专合字（2012）197号]，贵州省科学技术基金[黔科合J字（2012）2091号]. |
|
| Effect of β-asarone on differential protein expression in brain tissue of APPswe/PS1dE9 double transgenic mice |
| GUO Li-li1,2*,WANG Yu-jun3,AO Jun-wen3,GUO Yan-li2 |
(1. Department of Pathology, The Second Hospital Affiliated to Guiyang University of Chinese Medicine, Guiyang 550002, Guizhou, China;
2. Department of Pathology, The First People's Hospital of Guiyang, Guiyang 550002, Guizhou, China;
3. Department of Pathology, School of Basic Medicine, Guizhou Medical University, Guiyang 550004, Guizhou, China
*Corresponding author) |
| Abstract: |
| Objective To investigate the effect of β-asarone on differential protein expression in brain tissue of APPswe/PS1dE9 double transgenic mice, and to explore its mechanism in treatment of Alzheimer disease (AD). Methods The animals were divided into normal control group (C57BL/6J mice), model group (APPswe/PS1dE9 mice) and β-asarone treatment group (APPswe/PS1dE9 mice), with ten mice in each group. In a period of 90 days, the mice in β-asarone treatment group were administered with β-asarone by intragastric gavage (15 mg/[kg·d]), and the mice in normal control and model groups were administered with equal doses of normal saline. The learning and memory abilities of mice were detected by Morris water maze test. The expression of β-amyloid precursor protein (APP) in brain tissues was detected by immunohistochemistry. Proteomics analysis of brain tissues was performed by isobaric tags for relative and absolute quantification (iTRAQ). The expression of differential protein H2A and H2B was identified by Western blotting. Results Compared with the model group, the escape latency and the first latency time required to find the escaped platform of mice in the β-asarone treatment group were significantly shortened (P<0.05), the across-platform times were significantly increased (P<0.05), the expression of APP was significantly decreased (P<0.05), and the expressions of H2A 1-H, H2B 2-E and H2B 1-F/J/L were significantly decreased (P<0.05). Conclusion β-Asarone plays a therapeutic role by intervening the modification of histone, which might be one of the mechanisms to improve learning and memory abilities injured by the toxicity of β-amyloid peptide. |
| Key words: Alzheimer disease β-asarone double transgenic mice histones protein modification |
