人脐带间充质干细胞联合莱菔硫烷对阿尔茨海默病转基因小鼠治疗作用的初步研究

Preliminary study on the therapeutic effect of human umbilical cord mesenchymal stem cells with or without sulforaphane on transgenic mice of Alzheimer's disease

目的:探索人源性脐带间充质干细胞(hUC-MSCs)或莱菔硫烷(sulforaphane,SFN)单独或联合应用对阿尔茨海默病(Alzheimer’s disease,AD)转基因小鼠脑内生物标志物的影响,并为AD治疗策略或进一步研究提供依据。方法:将24只8周龄雄性APP/PS1转基因小鼠随机分为4组,分别接受PBS、SFN、hUC-MSCs单用或与SFN联合治疗。药物腹腔内注射、间充质干经细胞脑室注入,14天后处死小鼠,取大脑进行免疫荧光染色和蛋白质印迹分析。结果:hUC-MSCs和SFN单独或联合使用均能降低大脑皮层Aβ和Tau蛋白水平,联合使用效果更显著。结论:本研究动物实验初步结果见AD主要两个生物标志物Aβ和Tau蛋白下调,提示hUC-MSCs与SFN联合应用可能有效治疗早期AD,这表明SFN和hUCMSCs的联合治疗可能是治疗AD的一种新颖、有效的策略,需要进一步研究。

Objective:To explore the effects of human umbilical cord mesenchymal stem cells(hUC-MSCs)with or without sulforaphane(SFN)on the biomarkers of the brain from APP/PS1 transigenic mice of Alzheimer's disease(2xTg-AD mice),and to provide a basis for further study or treatment strategies to AD.Methods:8-week-old males,24 APP/PS1 transgenic mice were randomly divided into four groups and respectively treated with PBS,SFN,hUC-MSCs,or hUC-MSCs with SFN.The cells were injected into the ventricles of the brain while SFN was delivered by i.p.to 2xTg-AD mice.The mice were euthanized at 14 days after the treatment.Aβ,Tau as biomarkers of AD in the brains,were subjected to immunofluorescence staining and Western Blot Analysis.Results:hUC-MSCs or SFN could downregulate the levels of Aβor Tau protein in the cerebral cortex,with a better effect when they were used at the same time to 2xTg-AD mice.Conclusion:The application of hUC-MSCs with SFN may have a good therapeutic effect on early AD,and further study be needed.