中国组织工程研究

中国组织工程研究 ›› 2010, Vol. 14 ›› Issue (37): 6917-6921.doi: 10.3969/j.issn.1673-8225.2010.37.018

• 组织构建实验造模 experimental modeling in tissue construction • 上一篇    下一篇

β淀粉样蛋白1-40和氯化铝双干预阿尔茨海默病大鼠模型的建立

刘志安1，2，赵娓娓3，马  凯4，吕春娥2，徐铁军1，2   

  1. 徐州医学院，1江苏省脑病生物信息重点实验室，  2人体解剖学和神经生物学教研室，4计算机教研室，江苏省徐州市 221002；3解放军第四军医大学附属西京医院放射科，陕西省西安市 710032
  • 出版日期:2010-09-10 发布日期:2010-09-10
  • 通讯作者: 徐铁军，博士，教授，博士生导师，徐州医学院解剖学和神经生物学教研室，徐州医学院研究生学院院长。徐州医学院，江苏省脑病生物信息重点实验室，人体解剖学和神经生物学教研室，江苏省徐州市 221002 xztjxu@163.com
  • 作者简介:刘志安☆，男，1970年生，江苏省徐州市人，汉族，南京医科大学在读博士，副教授，硕士生导师，主要从事阿尔茨海默病的基础和应用基础研究。 zhianliu@126.com
  • 基金资助:

    江苏省脑病生物信息重点实验室开放课题(JSBL0903)“NMDA受体亚单位NR1、NR2A和NR2B在模型大鼠阿尔茨海默病发生机制中的作用”；江苏省研究生科研创新计划项目(苏教研[2009]10号)“NMDARs在阿尔茨海默病大鼠海马表达及其作用的研究”；江苏省高校自然科学基金项目(07KJB310117)“应用脑电提取脑内特异性核团功能信息的研究”。

Establishment of a Alzheimer’s disease rat model intervened by beta-amyloid protein 1-40 and aluminum chloride

Liu Zhi-an 1, 2, Zhao Wei-wei3, Ma Kai4, Lü Chun-e2, Xu Tie-jun 1, 2   

  1. 1 Jiangsu Province Key Laboratory of Brain Disease Bioinformation, 2 Department of Anatomy and Neurobiology, 4 Department of Computer, Xuzhou Medical College, Xuzhou  221002, Jiangsu Province, China; 3 Department of Radiology, Affiliated Xijing Hospital of Fourth Military Medical University, Xi’an  710032, Shaanxi Province, China　
  • Online:2010-09-10 Published:2010-09-10
  • Contact: Xu Tie-jun, Doctor, Professor, Doctoral supervisor, Jiangsu Province Key Laboratory of Brain Disease Bioinformation, Department of Anatomy and Neurobiology, Xuzhou Medical College, Xuzhou 221002, Jiangsu Province, China xztjxu@163.com
  • About author:Liu Zhi-an☆, Studying for doctorate, Associate professor, Master’s supervisor, Jiangsu Province Key Laboratory of Brain Disease Bioinformation, Department of Anatomy and Neurobiology, Xuzhou Medical College, Xuzhou 221002, Jiangsu Province, China zhianliu@126.com
  • Supported by:

     the Open Research Fund Program of the Jiangsu Key Laboratory of Brain Disease Bioinformation, No. JSBL0903*; Program for Postgraduates Research Innovattion in University of Jiangsu Province, No. [2009]10*; Natural Science Foundation of Colleges and Universities in Jiangsu Province, No. 07KJB310117*

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摘要：

背景：目前已建立的各种阿尔茨海默病动物模型均存在一定的局限性。
目的：以β淀粉样蛋白1-40和氯化铝双干预的方式，建立一种较为理想而实用的阿尔茨海默病大鼠模型。
方法：健康雄性老年SD大鼠，经Morris水迷宫训练和筛选后，随机分为模型组、生理盐水组和对照组。采用单侧侧脑室一次性注射β淀粉样蛋白1-40和腹腔连续4周隔天注射3%氯化铝的方式建立阿尔茨海默病大鼠模型。以Morris水迷宫实验和跳台实验检测模型大鼠的行为学变化。以刚果红和苏木精-伊红染色检测大鼠海马淀粉样蛋白沉积以及病理学改变。
结果与结论：与对照组及生理盐水组相比，模型组大鼠水迷宫实验逃避潜伏期明显延长(P < 0.05)；跳台实验反应时间、基础错误次数和错误次数显著增加(P < 0.05)，潜伏期明显缩短(P < 0.05)。模型组大鼠海马可见淀粉样蛋白物质沉积，细胞形态发生明显的损伤改变且细胞数量减少。以上结果提示，以β淀粉样蛋白1-40和氯化铝双干预的方式能够成功复制出一种比较理想而实用的阿尔茨海默病大鼠模型。

关键词: 氯化铝, &beta, 淀粉样蛋白1-40, 阿尔茨海默病, 大鼠, 动物模型

Abstract:

BACKGROUND: The existed Alzheimer's disease (AD) animal models have certain limitations.
OBJECTIVE: To establish an ideal and practical AD rat model intervened by β-amyloid protein-40 (Aβ1-40) and AlCl3.
METHODS: Healthy male aged Sprague Dawley rats were randomly divided into AD model group, saline group and normal control group after Morris water maze training and screening. Rat AD models were established by one-time unilateral intracerebroventricular injection of Aβ1-40 and continuous intraperitoneal injection of AlCl3 every other day for 4 weeks. The behavioral changes of model rats were detected by Morris water maze test and step-down test. The hippocampal amyloid deposition and pathology changes of rats were determined by Congo red and hematoxylin-eosin staining.
RESULTS AND CONCLUSIONS: Compared with the normal control group and saline group, the water maze test escape latency of model group rats was significantly longer (P < 0.05). The reaction time, basal number of errors, and number of errors of step-down test were increased significantly (P < 0.05). The latency period of step-down test was shortened significantly (P < 0.05). The amyloid substance deposition, as well as the obvious damage changes in morphology and reduction of cells number could be seen in hippocampus of model group rats. These results suggest that an ideal and practical AD rat model can be successfully established with Aβ1-40 and AlCl3.

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