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  

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

作　　者：高明龙[1] 史少霞 张坤 张英东[1] 李娜[1] 余明[1] 王永良[1,2] Gao Ming-long;Shi Shao-xia;Zhang Kun;Zhang Ying-dong;Li Na;Yu Ming;Wang Yong-liang(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)

机构地区：[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

出　　处：《中国组织工程研究》2018年第9期1419-1424,共6页Chinese Journal of Tissue Engineering Research

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

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);(3)BDNF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。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 transplanta

关 键 词：羊膜 间质干细胞移植 脑源性神经营养因子 阿尔茨海默病 学习 记忆 受体 神经生长因子 组织工程 

分 类 号：R394.2[医药卫生—医学遗传学]