[1]杨 璐),李庆华)#,许 玲),等.粪菌移植对阿尔茨海默病小鼠学习记忆能力的影响*[J].郑州大学学报(医学版),2017,(06):702-706.[doi:10.13705/j.issn.1671-6825.2017.06.010]
 YANG Lu),LI Qinghua),XU Ling),et al.Effects of fecal microbiota transplantation on learning and memory ability of Alzheimer's disease mice[J].JOURNAL OF ZHENGZHOU UNIVERSITY(MEDICAL SCIENCES),2017,(06):702-706.[doi:10.13705/j.issn.1671-6825.2017.06.010]
点击复制

粪菌移植对阿尔茨海默病小鼠学习记忆能力的影响*()
分享到:

《郑州大学学报(医学版)》[ISSN:1671-6825/CN:41-1340/R]

卷:
期数:
2017年06期
页码:
702-706
栏目:
论著
出版日期:
2017-11-15

文章信息/Info

Title:
Effects of fecal microbiota transplantation on learning and memory ability of Alzheimer's disease mice
作者:
杨 璐1)李庆华1)#许 玲1)刘雯雯1)刘艳霞1)黄团结1)邢 衢1)李 鹏1)张 乐1)关方霞12)#
1)郑州大学生命科学学院 郑州 450001
2)郑州大学第一附属医院干细胞研究室 郑州 450052
Author(s):
YANG Lu1) LI Qinghua1) XU Ling1) LIU Wenwen1) LIU Yanxia1) HUANG Tuanjie1) XING Qu1) LI Peng1) ZHANG Le1) GUAN Fangxia12)
1)College of Life Sciences, Zhengzhou University, Zhengzhou 450001
2)Stem Cell Laboratory, the First Affiliated Hospital, Zhengzhou University, Zhengzhou 450052
关键词:
小鼠 阿尔茨海默病 粪菌移植 肠道菌群 β淀粉样蛋白
Keywords:
mouse Alzheimer's disease fecal microbiota transplantation gut microbiota amyloid β-protein
分类号:
R592
DOI:
10.13705/j.issn.1671-6825.2017.06.010
摘要:
目的:观察粪菌移植(FMT)对阿尔茨海默病模型小鼠(APP+转基因小鼠)学习记忆能力及脑内β淀粉样蛋白(Aβ)沉积的影响。方法:将15只小鼠分为APP-组、APP+组、FMT组,每组5只。对FMT组APP+小鼠进行FMT,每天1次,连续4周,APP+组及APP-组用生理盐水灌肠处理。4周后,通过Morris水迷宫实验观察各组小鼠认知能力和学习记忆能力; 采用Western blot法检测小鼠脑组织中衰老相关蛋白(P21、P53、Sirt1、Sirt2、PCNA)的表达情况; 采用刚果红染色法观察小鼠脑内Aβ沉积的变化情况。结果:与APP-组相比,APP+组小鼠逃避潜伏期延长,穿越平台次数减少,目标象限停留时间减少(P<0.05)。经FMT处理后,FMT组小鼠与APP+组小鼠相比,逃避潜伏期缩短,穿越平台次数增多,目标象限停留时间延长,Aβ沉积减少,脑组织中衰老相关蛋白P21、P53表达减少,而Sirt1、Sirt2、PCNA表达增多(P<0.05)。结论:FMT 可以改善阿尔茨海默病小鼠的学习记忆能力,减缓衰老,减少脑组织Aβ沉积。
Abstract:
Aim: To study the effects of fecal microbiota transplantation(FMT)on learning and memory ability and amyloid β-protein(Aβ)deposition in Alzheimer's disease mice.Methods: A total of 15 mice were randomly allocated into APP- group, APP+ group, and FMT group(n=5). The APP+ mice in FMT group were treated with FMT for 4 weeks, while the mice in APP+ group and APP- group were enemaed with normal saline. The learning and memory ability of mice was tested by Morris water maze.And then Western blot was employed to detect the expression of senescence related proteins(P21, P53, Sirt1, Sirt2, PCNA)in mice brain tissue, and the change of Aβ deposition in the brain was observed by Congo red staining.Results: Compared with the APP- group, the escaping latency of the APP+ group was longer, while the times of crossing the platform quadrant was less and the time of spending in the target quadrant was shorter(P<0.05). After FMT, the escaping latency of the mice was decreased, the times of crossing the platform quadrant and the time of spending in the target quadrant were increased(P<0.05). And the deposition of Aβ in brain tissue of FMT group was reduced compared with the APP+ group(P<0.05). Additionally, the expressions of P21 and P53 in brain tissue of FMT group reduced, and the expressions of Sirt1, Sirt2 and PCNA increased significantly(P<0.05).Conclusion: FMT could improve the learning and memory ability of Alzheimer's disease mice by slowing down its aging and reducing the formation of Aβ deposition in brain.

参考文献/References:

[1] LEUZY A,ZIMMER ER,GAUTHIER SA.Amyloid imaging in Alzheimer's disease: a potential new era of personalized medicine?[J].Transl Neurosci,2014,5(1):51
[2] SHISHIDO H,KISHIMOTO Y,KAWAI N,et al.Traumatic brain injury accelerates amyloid-β deposition and impairs spatial learning in the triple-transgenic mouse model of Alzheimer's disease[J].Neurosci Lett,2016,629(6):62
[3] 孟楠,马珊珊,王欣欣,等.氯化锂联合 hUC-MSCs移植对阿尔茨海默病小鼠的治疗作用[J].郑州大学学报(医学版),2016,51(2):157
[4] 周珂新,徐雷艇,马银娟,等.阿尔茨海默病与肠道菌群的关系及菌群调节对其防治的展望[J].中国药理学与毒理学杂志,2016,30(11):1198
[5] MARANDUBA CM,DE CASTRO SB,DE SOUZA GT,et al.Intestinal microbiota as modulators of the immune system and neuroimmune system: impact on the host health and homeostasis[J].J Immunol Res,2015,2015:931574
[6] 马玉帛,李婷宇,曹海超,等.粪菌移植的临床研究进展[J].中华消化病与影像杂志:电子版,2016,6(1):28
[7] 江学良,崔云龙,张宗梅,等.粪菌移植的研究现状、存在问题与发展方向[J].中华消化病与影像杂志:电子版,2014,4(4):152
[8] 施新猷.医用实验动物学[M].西安:陕西科学技术出版社,1989:51
[9] 莫睿,魏智民,杨云生.抗衰老机制研究进展[J].解放军医学杂志,2017,42(8):743
[10]张发明.粪菌移植的概念、历史、现状和未来[J].中国内镜杂志,2012,18(9):930
[11]MOHAMED T,SHAKERI A,RAO PP.Amyloid cascade in Alzheimer's disease:recent advances in medicinal chemistry[J].Eur J Med Chem,2016,113(10):258
[12]余静,楚佳梅,高灵爱,等.麦粒灸对阿尔茨海默病小鼠学习记忆能力及脑内淀粉样蛋白沉积的影响[J].针刺研究,2014,39(1):58
[13]邬佳瑜,罗蔓.肠道菌群与衰老关系的研究进展[J].中国临床医学,2014,21(6):745

相似文献/References:

[1]梁璐△,陈小军,吴昊,等.人脐带间充质干细胞在小鼠体内的迁移变化及宿主的免疫反应*[J].郑州大学学报(医学版),2010,(01):33.
 LIANG Lu,CHEN Xiaojun,WU Hao,et al.Survival and homing of human umbilical cord mesenchymal stem cells in immunocompetent mice[J].JOURNAL OF ZHENGZHOU UNIVERSITY(MEDICAL SCIENCES),2010,(06):33.
[2]许燕),高国伟),鄢文海),等.低速离心法分离小鼠胚胎干细胞*[J].郑州大学学报(医学版),2010,(01):75.
 XU Yan),GAO Guowei),YAN Wenhai),et al.A new method of mouse embryonic stem cells isolation[J].JOURNAL OF ZHENGZHOU UNIVERSITY(MEDICAL SCIENCES),2010,(06):75.
[3]郭艺红,孙莹璞#,乔玉环,等.不同用药方案对小鼠种植窗期子宫内膜白血病抑制因子及胞饮突表达的影响*[J].郑州大学学报(医学版),2010,(02):202.
 GUO Yihong,SUN Yingpu,QIAO Yuhuan,et al.Expression of LIF and pinopodes in mouse endometrium during the implantation window based on different treatment protocols[J].JOURNAL OF ZHENGZHOU UNIVERSITY(MEDICAL SCIENCES),2010,(06):202.
[4]符粤文))△,吴德沛),陈峰),等.单倍型骨髓移植小鼠移植物抗宿主病模型的建立及移植物抗宿主病靶器官T细胞受体克隆检测*[J].郑州大学学报(医学版),2009,(06):1171.
 FU Yuewen)),WU Depei),CHEN Feng),et al.Establishment of murine haploidentical bone marrow transplantation model and detection of T cell receptor clonal in target organs of graftversushost disease[J].JOURNAL OF ZHENGZHOU UNIVERSITY(MEDICAL SCIENCES),2009,(06):1171.
[5]唐蓓△.小鼠Arl8a基因逆转录病毒载体MSCVGFPArl8a的构建*[J].郑州大学学报(医学版),2009,(06):1204.
 TANG Bei.Cloning of mouse Arl8a gene and construction of its retroviral vector[J].JOURNAL OF ZHENGZHOU UNIVERSITY(MEDICAL SCIENCES),2009,(06):1204.
[6]杨雯雯),常树丽),李艳菲),等.氯化汞对小鼠睾丸间质瘤mLTC1细胞增殖和孕酮合成的影响[J].郑州大学学报(医学版),2009,(06):1253.
 YANG Wenwen),CHANG Shuli),LI Yanfei),et al.Effects of mercury chloride on cell growth and progesterone biosynthesis of mLTC1 cells[J].JOURNAL OF ZHENGZHOU UNIVERSITY(MEDICAL SCIENCES),2009,(06):1253.
[7]王红伟)△,范玲玲),任爱红),等.氯胺酮对小鼠离体十二指肠纵行肌条收缩的影响*[J].郑州大学学报(医学版),2009,(05):990.
 WANG Hongwei),FAN Lingling),REN Aihong),et al.Effect of ketamine on contraction of isolated duodenal longitudinal strips in mice[J].JOURNAL OF ZHENGZHOU UNIVERSITY(MEDICAL SCIENCES),2009,(06):990.
[8]张菊娥)△,陈小让),张翠英),等.四君子汤加柴胡对长期摄酒小鼠血脂及抗氧化作用的影响[J].郑州大学学报(医学版),2009,(05):1045.
 ZHANG Jue),CHEN Xiaorang),ZHANG Cuiying),et al.Effect of Sijun decoction with bupleurum falcatum on blood lipid and its antioxidation ability in alcoholintake mice[J].JOURNAL OF ZHENGZHOU UNIVERSITY(MEDICAL SCIENCES),2009,(06):1045.
[9]朱宝菊),乔玉环)#,李印).canstatin基因治疗对小鼠人卵巢癌移植瘤生长及Caspase3、Flk1蛋白表达的影响*[J].郑州大学学报(医学版),2009,(02):292.
 ZHU Baoju),QIAO Yuhuan),LI Yin).Effects of canstatin gene theraphy on expression of Flk1 and Caspase3 and growth of human ovarian cancer in mice[J].JOURNAL OF ZHENGZHOU UNIVERSITY(MEDICAL SCIENCES),2009,(06):292.
[10]刘青),刘剑波)#.干扰素γ对哮喘小鼠肺组织中水通道蛋白5表达的影响*[J].郑州大学学报(医学版),2009,(02):306.
 LIU Qing),LIU Jianbo).Effects of interferongamma on expression of aquaporin5 in lung tissue of asthmatic mice[J].JOURNAL OF ZHENGZHOU UNIVERSITY(MEDICAL SCIENCES),2009,(06):306.

备注/Memo

备注/Memo:
*国家自然科学基金资助项目 81471306; 河南省高校科技创新团队基金资助项目 15IRTSTHN022; 河南省科技创新人才计划基金资助项目 154200510008
#通信作者:关方霞,女,1969年2月生,博士,教授,研究方向:干细胞与再生医学,E-mail:guanfangxia@126.com; 李庆华,女,1983年6月生,博士,讲师,研究方向:微生物学,E-mail:guozilqh@126.com
更新日期/Last Update: 2017-11-20