β片层阻断肽联合人脐带间充质干细胞对APP转基因鼠的治疗作用  

The combined effects of β-sheet breaker and hUCMSC on APP transgenic mice

作　　者：孙凤仙[1] 王曼[1] 徐艳玲[1] 林来祥[2] 徐淑梅[1] 

机构地区：[1]天津医科大学生理学教研室,天津300070 [2]天津医科大学内分泌研究所,天津300070

出　　处：《中国应用生理学杂志》2013年第3期239-244,I0004,共7页Chinese Journal of Applied Physiology

基　　金：国家科技重大专项基金资助(2009ZX09103-029);天津市科技支撑重点项目基金资助(09ZCKFSH00100);天津市科技攻关培育项目基金资助(05YFGPGX07100)

摘　　要：目的:观察β片层阻断肽H102与人脐带间充质干细胞(hUCMSC)联合应用对APP转基因鼠行为学、脑内tau蛋白磷酸化、细胞凋亡及其相关酶表达的影响。方法:将APP转基因小鼠随机分为模型组、hUCMSC组、H102组、H102+hUCMSC组,并设同月龄同背景C57BL/6J小鼠为正常对照组。2周及4周后做Morris水迷宫实验检测AD小鼠的空间参考记忆的变化,利用免疫组织化学方法和Western blot方法测定脑内Bad、Bax、Bc-l 2、Bc-l x1、P-tau、GSK-3β、PP-2A及PP-1的表达。结果:hUCMSC 2周组学习记忆能力较模型组没有显著性差异。hUCMSC 4周组、H102及H102+hUCMSC组均明显提高AD模型鼠的学习记忆能力,显著抑制细胞凋亡、减少tau的过度磷酸化。结论:β片层阻断肽H102与hUCMSC联合应用对AD有一定的治疗作用。Objective： To study the effect of combining the injection of β-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-x1,P-tau,GSK-3β,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 learning and memory,and reduced the phosphorylation of tau and brain cell＇s apoptosis of the Alzheidiseas（AD） mice.Conclusion： β-sheet breaker H102 together with transplanting hUCMSC is an effective therapeutic strategy for AD.

关 键 词：H102 阿尔茨海默病 脐带间充质干细胞 APP转基因小鼠 MORRIS水迷宫 

分 类 号：R338.8[医药卫生—人体生理学]