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β-折叠破坏肽与脐带间充质干细胞联合作用于APP转基因小鼠的研究

[The combined effects of beta-sheet breaker and hUCMSC on APP transgenic mice].

作者信息

Sun Feng-Xian, Wang Man, Xu Yan-Ling, Lin Lai-Xiang, Xu Shu-Mei

机构信息

Department of Physiology, Tianjin Medical University, Tianjin 300070, China.

出版信息

Zhongguo Ying Yong Sheng Li Xue Za Zhi. 2013 May;29(3):239-44.

PMID:23940958
Abstract

OBJECTIVE

To study the effect of combining the injection of beta-sheet breaker H102 with human umbilical cord mesenchymal stem cell (hUCMSC) on APP transgenic mice behavior, P-tau, apoptosis and the expression of relevant enzymes in the brain.

METHODS

APP transgenic mice were randomly divided into model group, hUCMSC group, H102 group, H102 with hUCMSC group and a group of C57BL/6J mice with the same age and background was set as normal. After two weeks and four weeks, the ability of spatial reference memory was tested by Morris Water Maze. After four weeks, immunohistochemical stain and Western blot were done to detect the content of Bad, Bax, Bcl-2, Bcl-xl, P-tau, GSK-3beta, PP-2A and PP-1 in mice brain.

RESULTS

The ability of memory of hUCMSC in 2 weeks group was slightly improved than that in the model group. hUCMSC in four weeks group, H102 group and H102 with hUCMSC group significantly improved the ability of and memory, and reduced the phosphorylation of tau and brain cell's apoptosis of the Alzheimer disease (AD) mice.

CONCLUSION

Beta-sheet breaker H102 together with transplanting hUCMSC is an effective therapeutic strategy for AD.

摘要

目的

研究β-折叠破坏肽H102与人脐带间充质干细胞(hUCMSC)联合注射对APP转基因小鼠行为、P- tau蛋白、细胞凋亡及脑内相关酶表达的影响。

方法

将APP转基因小鼠随机分为模型组、hUCMSC组、H102组、H102与hUCMSC联合组,并设同龄同背景的C57BL/6J小鼠为正常组。两周和四周后,通过Morris水迷宫检测空间参考记忆能力。四周后,进行免疫组织化学染色和蛋白质免疫印迹法检测小鼠脑内Bad、Bax、Bcl-2、Bcl-xl、P- tau、GSK-3β、PP-2A和PP-1的含量。

结果

2周龄hUCMSC组小鼠的记忆能力较模型组略有改善。4周龄hUCMSC组、H102组及H102与hUCMSC联合组显著改善了阿尔茨海默病(AD)小鼠的记忆能力,降低了tau蛋白磷酸化水平及脑细胞凋亡。

结论

β-折叠破坏肽H102与移植hUCMSC联合应用是治疗AD的有效策略。

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Effects of mesenchymal stem cells transplantation on cognitive deficits in animal models of Alzheimer's disease: A systematic review and meta-analysis.间充质干细胞移植对阿尔茨海默病动物模型认知功能障碍的影响:系统评价和荟萃分析。
Brain Behav. 2018 Jul;8(7):e00982. doi: 10.1002/brb3.982. Epub 2018 Jun 6.