中国组织工程研究

中国组织工程研究 ›› 2010, Vol. 14 ›› Issue (45): 8421-8425.doi: 10.3969/j.issn.1673-8225.2010.45.015

• 干细胞移植 stem cell transplantation • 上一篇    下一篇

脑源性神经营养因子基因修饰骨髓间质干细胞移植痴呆大鼠大脑皮质及海马tau蛋白、β-淀粉样蛋白及神经元超微结构的变化　

魏昌秀1，代  宏1，陈松林2　   

  1. 1贵州省人民医院神经内科，贵州省贵阳市 550002；2中山大学黄埔医院神经内科，广东省广州市  510700
  • 出版日期:2010-11-05 发布日期:2010-11-05
  • 作者简介:魏昌秀☆，女，1973年生，贵州省毕节市人，汉族，2004年中山大学毕业，博士，副主任医师，主要从事痴呆、脑血管病方面的研究。 weichangxiu@yahoo.com.cn
  • 基金资助:

    贵州省优秀科技人才省长基金项目(黔省专合字(2005)231号)。

Effects of bone marrow mesenchymal stem cells modified with brain-derived neurotrophic factor gene on tau protein, beta-amyloid and neuronal ultrastructure in the cerebral cortex and hippocampus of an Alzheimer’s disease rat 

Wei Chang-xiu1, Dai Hong1, Chen Song-lin2   

  1. 1 Department of Neurology, Guizhou People’s Hospital, Guiyang  550002, Guizhou Province, China; 2 Department of Neurology, Huangpu Hospital, Sun Yat-sen University, Guangzhou  510700, Guangdong Province, China
  • Online:2010-11-05 Published:2010-11-05
  • About author:Wei Chang-xiu☆, Doctor, Associate chief physician, Department of Neurology, Guizhou People’s Hospital, Guiyang 550002, Guizhou Province, China weichangxiu@yahoo.com.cn
  • Supported by:

     the Nomarch Foundation Program of Excellent Science and Technology Talents of Guizhou Province, No. (2005)231*

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摘要：

背景：课题组前期的研究表明，重组脑源性神经营养因子基因修饰的骨髓间质干细胞脑内移植可以改善阿尔茨海默病鼠的认知功能。
目的：观察脑源性神经营养因子基因修饰的骨髓间充质干细胞移植对阿尔茨海默病鼠大脑皮质及海马tau蛋白磷酸化、β-淀粉样蛋白及海马CA1区神经元超微结构的影响。
方法：采用侧脑室立体定向注射β-淀粉样肽建立阿尔茨海默病动物模型，取单纯或经脑源性神经营养因子基因修饰的骨髓间质干细胞移植，1个月后采用Western bloting 方法检测大脑皮质及海马组织总tau蛋白及磷酸化的tau蛋白表达，以ELISA方法检测β-淀粉样蛋白40，β-淀粉样蛋白42含量，同时透射电镜观察海马CA1区神经元超微结构的变化。
结果与结论： ①脑源性神经营养因子修饰的骨髓间质干细胞能够降低大脑皮质及海马组织总tau蛋白及磷酸化的tau蛋白表达，降低大脑皮质及海马β-淀粉样蛋白40和β-淀粉样蛋白42表达。②模型组大鼠海马CA1区神经元出现粗面内质网扩张、膜断裂，线粒体数目减少、线粒体肿胀、核膜不清等改变，脑源性神经营养因子基因修饰的骨髓间质干细胞对上述改变有减轻作用，较骨髓间质干细胞未修饰组明显。

关键词: 骨髓间充质干细胞, 脑源性神经营养因子, 基因修饰, 阿尔茨海默病, tau, &beta, -淀粉样蛋白

Abstract:

BACKGROUND: Our previous studies indicted that bone marrow mesenchymal stem cells (BMSCs) modified by brain-derived neurotrophic factor (BDNF) gene could ameliorate the memory function of Alzheimer’s disease (AD) rat.
OBJECTIVE: To observe the effect of BDNF gene-modified BMSCs transplantation on tau protein phosphorylation and beta-amyloid (Aβ) in the cerebral cortex and hippocampus, and neuron ultrastructure in the hippocampal CA1 region of AD model rat.
METHODS: After AD models were established by Aβ stereotactic injection into lateral cerebral ventricle, BDNF modified and unmodified BMSCs were implanted into AD model. One month after transplantation, the expressions of total tau protein and tau hyperphosphrylation in cerebral cortex and hippocampus were detected using Western blotting method. Aβ 40 and Aβ 42 were detected by enzyme-linked immunosorbent assay, and the hippocampal CA1 neuron ultrastructures were observed via transmission electron microscope.
RESULTS AND CONCLUSION: BDNF-modified BMSCs could decrease expression of total tau protein and tau hyperphosphrylation in the cerebral cortex and hippocampus and reduce Aβ 40 and Aβ 42 expression in the cerebral cortex and hippocampus. In AD model group, there were obvious degeneration of organells, such as disruption of rough endoplasmic reticulum, reduction of ribosome, mitochondrial swelling, blurred nuclear membrane. BDNF-modified BMSCs could reduce above-described changes. Its effect was more significant than unmodified BMSCs group.

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