中国组织工程研究 ›› 2018, Vol. 22 ›› Issue (9): 1419-1424.doi: 10.3969/j.issn.2095-4344.0474

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

脑源性神经营养因子修饰人羊膜间充质干细胞移植改善老年痴呆大鼠的学习记忆能力

高明龙1,史少霞1,张 坤1,张英东1,李 娜1,余 明1,王永良1,2   

  1. 1河北医科大学第一医院精神科,河北省石家庄市 050031;2河北省精神卫生研究所/河北省脑老化与认知精神科学重点实验室,河北省石家庄市 050031
  • 修回日期:2018-01-19 出版日期:2018-03-28 发布日期:2018-04-03
  • 通讯作者: 王永良,硕士,主治医师,河北医科大学第一医院精神科 河北省石家庄市 050031;河北省精神卫生研究所/河北省脑老化与认知精神科学重点实验室,河北省石家庄市 050031
  • 作者简介:高明龙,男,1978年生,山东省茌平县人,主治医师,2003年齐齐哈尔医学院毕业,硕士,主要从事老年疾病研究。
  • 基金资助:

    河北省卫生厅科学研究项目(ZL20140099);河北省卫生厅项目(20130578)

Effects of brain-derived neurotrophic factor-modified human amniotic membrane-derived mesenchymal stem cell transplantation on learning and memory abilities of Alzheimer's disease rats

Gao Ming-long1, Shi Shao-xia1, Zhang Kun1, Zhang Ying-dong1, Li Na1, Yu Ming1, Wang Yong-liang1, 2   

  1. 1Department of Psychiatry, First Affiliated Hospital of Hebei Medical University, Shijiazhuang 050031, Hebei Province, China; 2Hebei Provincial Institute of Mental Health/ Hebei Provincial Key Laboratory of Aging and Cognitive Psychology, Shijiazhuang 050031, Hebei Province, China
  • Revised:2018-01-19 Online:2018-03-28 Published:2018-04-03
  • Contact: Wang Yong-liang, Master, Attending physician, Department of Psychiatry, First Affiliated Hospital of Hebei Medical University, Shijiazhuang 050031, Hebei Province, China; Hebei Provincial Institute of Mental Health/Hebei Provincial Key Laboratory of Aging and Cognitive Psychology, Shijiazhuang 050031, Hebei Province, China
  • About author:Gao Ming-long, Master, Attending physician, Department of Psychiatry, First Affiliated Hospital of Hebei Medical University, Shijiazhuang 050031, Hebei Province, China
  • Supported by:

    the Scientific Research Project of Hebei Provincial Health Department, No. ZL20140099; the project funded by the Hebei Provincial Health Department, No. 20130578

摘要:

文章快速阅读:

文题释义:
脑源性神经营养因子:
是1982年Barde等首先在猪脑中发现的一种具有神经营养作用的蛋白质。脑源性神经营养因子及其受体在神经系统广泛表达。脑源性神经营养因子分布在中枢神经系统、周围神经系统、内分泌系统、骨和软骨组织等广泛区域内,但主要是在中枢神经系统内表达,其中海马和皮质的含量最高。
NGF受体:根据其糖蛋白与凝集素结合能力不同分为两型。Ⅰ型为高亲和力受体(TrkA),是由原癌基因Trk编码的酪氨酸激酶受体,主要分布在神经元细胞膜上,少量在胞浆内。Ⅱ型为低亲和力受体(p75),它与所有的神经营养因子以相似的亲和力结合,在成年大鼠和正常人脑中p75及其mRNA主要在基底前脑和海马表达。p75能够增强TrkA对NGF结合的亲和力和特异性,协助NGF/TrkA的逆行运输,同时也参与神经元凋亡的调控。

 

摘要
背景:
研究发现多种干细胞治疗老年痴呆大鼠效果显著,但关于脑源性神经营养因子(brain-derived neurotrophic factor,BDNF)修饰人羊膜间充质干细胞移植治疗老年痴呆的研究报道较少。
目的:探讨BDNF修饰人羊膜间充质干细胞移植对老年痴呆大鼠学习记忆能力的影响。
方法:将48只SD大鼠根据随机数字法分为对照组、模型组、干细胞移植组和BDNF修饰干细胞移植组,每组12只。后3组建立老年痴呆大鼠模型,干细胞移植组和BDNF修饰干细胞移植组大鼠基底前脑注射人羊膜间充质干细胞和BDNF修饰人羊膜间充质干细胞。移植后2周,大鼠在三等份辐射式迷宫箱中检测学习记忆能力,免疫组化染色结合图像分析测定p75 NGFR阳性神经元数目。
结果与结论:①模型组、干细胞移植组、BDNF修饰干细胞移植组斜角带和内侧隔核p75 NGFR阳性神经元数均低于对照组(P < 0.05),干细胞移植组、BDNF修饰干细胞移植组斜角带和内侧隔核p75 NGFR阳性神经元数均高于模型组(P < 0.05),BDNF修饰干细胞移植组斜角带和内侧隔核p75 NGFR阳性神经元数高于干细胞移植组(P < 0.05);②模型组、干细胞移植组、BDNF修饰干细胞移植组大鼠的学习记忆能力均低于对照组(P < 0.05),干细胞移植组、BDNF修饰干细胞移植组大鼠的学习记忆能力均高于模型组(P < 0.05),BDNF修饰干细胞移植组大鼠的学习记忆能力高于干细胞移植组(P < 0.05);③BDNF修饰干细胞移植组大鼠的学习次数与p75 NGFR阳性神经元数呈负相关(P < 0.05),记忆能力与p75 NGFR阳性神经元数呈正相关(P < 0.05);④结果表明,人羊膜间充质干细胞移植可提高老年痴呆大鼠的学习记忆能力,BDNF修饰人羊膜间充质干细胞可进一步提高人羊膜间充质干细胞的治疗效果。

中国组织工程研究杂志出版内容重点:干细胞;骨髓干细胞;造血干细胞;脂肪干细胞;肿瘤干细胞;胚胎干细胞;脐带脐血干细胞;干细胞诱导;干细胞分化;组织工程
ORCID:
0000-0002-0545-594X(高明龙)

关键词: 脑源性神经营养因子, 羊膜间充质干细胞, 细胞移植, 老年痴呆, 学习, 记忆, p75 NGFR, 干细胞

Abstract:

BACKGROUND: A variety of stem cells have been found to be effective in the treatment of Alzheimer's disease in rats. However, few reports have been reported on the treatment of Alzheimer's disease rats with brain-derived neurotrophic factor (BDNF)-modified human amniotic membrane-derived mesenchymal stem cells.
OBJECTIVE: To investigate the effects of BDNF-modified human amniotic membrane-derived mesenchymal stem cell transplantation on the learning and memory abilities of Alzheimer's disease rats.
METHODS: Forty-eight Sprague-Dawley rats were divided into control group (no treatment), model group (Alzheimer's disease model), stem cell transplantation group (human amniotic membrane-derived mesenchymal stem cell transplantation+Alzheimer's disease model) and BDNF-modified stem cell transplantation group (BDNF-modified human amniotic membrane-derived mesenchymal stem cell transplantation+Alzheimer's disease model), 12 rats in each group. Learning and memory of model rats were determined in a trisection radiation maze and immunohistochemical staining was used to determine the number of p75 positive neurons at 2 weeks after cell transplantation.
RESULTS AND CONCLUSION: The number of p75 positive neurons in the bevel zone and medial septal nucleus was ranked as follows: the model group < the stem cell transplantation group < the BDNF-modified stem cell transplantation group < the control group, and there were significant differences among groups (P < 0.05). The learning and memory abilities of the rats were ranked as follows: the model group < the stem cell transplantation group < the BDNF-modified stem cell transplantation group < the control group, and there were significant differences among groups (P < 0.05). In the BDNF-modified stem cell transplantation group, the number of learnings was negatively correlated with the number of p75 NGFR-positive neurons (P < 0.05), while the memory capacity was positively correlated with the number of p75 NGFR-positive neurons (P < 0.05). These findings reveal that human amniotic membrane-derived mesenchymal stem cell transplantation can improve learning and memory abilities of Alzheimer's disease rats, and BDNF-modified human amniotic membrane-derived mesenchymal stem cells can further improve this therapeutic effect.

中国组织工程研究杂志出版内容重点:干细胞;骨髓干细胞;造血干细胞;脂肪干细胞;肿瘤干细胞;胚胎干细胞;脐带脐血干细胞;干细胞诱导;干细胞分化;组织工程

Key words: Amnion, Mesenchymal Stem Cell Transplantation, Brain-Derived Neurotrophic Factor, Alzheimer Disease, Learning, Memory, Receptor, Nerve Growth Factor, Tissue Engineering

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