阿尔茨海默病树鼩模型建立的探索
Establishment of the Alzheimer's Disease Model in Tupaia belangeri

中文摘要： 目的 探索建立树鼩阿尔茨海默病(AD)动物模型的可行性。 方法 将30只成年雄性树鼩 Tupaia belangeri随机分成3组,模型组腹腔注射D-半乳糖(D-gal)造成急性衰老后,对树鼩双侧海马内一次性注射β淀粉样蛋白1~42片段(Aβ1~42)和鹅膏蕈氨酸(IBO)的混合液,对照(生理盐水)组将所有药物替换为等剂量生理盐水,空白组不做处理。用Morris水迷宫对3组树鼩进行行为学测试,用苏木精-伊红染色法和镀银染色法进行病理检测分析。 结果 Morris水迷宫测试结果提示,模型树鼩出现了明显的学习记忆功能障碍。病理检测结果显示,模型组脑海马区出现明显胶质细胞增生和神经纤维缠结。对照组和空白组无明显病理改变。 结论 腹腔注射D-gal,双侧海马注射Aβ1~42和IBO混合液的方法可以造成树鼩学习记忆能力下降,并出现神经胶质细胞增生和神经纤维缠结,是一种可行的树鼩AD模型造模方法。
英文摘要： Objective To explore the feasibility of establishing Alzheimer's disease (AD) animal model with tree shrew ( Tupaia belangeri). Method 30 adult male tree shrews were randomly divided into three groups. Intraperitoneal injection of D-galactose (D-gal) was made to the model group causing acute aging, then the mixture of amyloid protein β1~42 fragment (Aβ1~42) and ibotenic acid (IBO) was injected once into the bilateral hippocampus of the tree shrews; all those drugs were replaced with normal saline in equivalent doses for the control group, while no treatment was done to the blank group. Then behavioral test was conducted to the three groups of tree shrew through Morris water maze, and pathological detection and analysis was made through HE staining and silver impregnation staining. Result Morris water maze test suggested that significant learning and memory dysfunction occurred on the model tree shrews. The pathological detection indicated that significant gliosis and neurofibrillary tangles occurred at the cerebral hippocampus of the model group. No significant pathological changes happened on the control group and the blank group. Conclusion Intraperitoneal injection of D-gal and injection of the mixture of Aβ1~42 and IBO into the bilateral hippocampus would cause decline in learning and memory ability of the tree shrews, as well as gliosis and neurofibrillary tangles, thus it was a feasible modeling method of AD model with tree shrew. 2016,(35): 270-274 收稿日期：2015-09-17 DOI：10.11984/j.issn.1000-7083.20150284 分类号：Q95-33 基金项目：国家自然科学基金项目(31560612); 广西科技基础条件平台建设项目(12-97-23);广西自然科学基金回国基金项目(2012GXNSFCA053005);广西自然科学基金面上项目(2013GXNSFAA019147) 作者简介：欧阳轶强(1977-), 博士研究生, 从事人类疾病动物模型研究 *通讯作者：郭松超, 博士生导师, 研究方向:营养与疾病, 实验动物学, E-mail:2433164518@qq.com 参考文献： 何保丽, 角建林, 李波, 等. 2013. 天麻素对老年痴呆树鼩海马BDNF 表达的影响[J]. 昆明医科大学学报, (9): 29-30. 刘学凤, 李义松, 冯丽谦, 等. 2012. 阿尔茨海默病大鼠模型复制的实验研究[J]. 中医学报, 27(175): 1606-1608. 武聪, 庄莹, 李艳茹, 等. 2012. 人参皂苷Rg2对阿尔茨海默病模型大鼠海马神经元结构及突触素表达的影响[J]. 中国老年学杂志, 3(32): 989-992. 许凌, 范宇, 蒋学龙, 等. 2013. 树鼩进化分类地位的分子证据[J]. 动物学研究, 34(2): 70-76. 李文德, 吴玉娥, 闵凡贵, 等. 2010. 颅内注射淀粉样β蛋白片段1-42和thiorphan对恒河猴脑内淀粉样β蛋白表达的影响[J]. 中国药理学与毒理学杂志, 2(24): 89-95. 杨文光. 1990.