阿尔茨海默病转基因小鼠脑内细胞因子动态水平分析研究

Dynamic level of cytokines in the brain of APP/PS1 transgenic mice

目的:天然免疫功能异常可能是导致阿尔茨海默病(Alzheimer’s disease, AD)的重要致病机制之一。本文旨在研究AD小鼠小胶质细胞早期极化失调的动态水平。方法:用电化学发光(mesoscale discovery, MSD)方法检测AD双转基因小鼠APPswe/PS1?E9(APP/PS1)小胶质细胞活化相关多种细胞因子(TNF-?、IL-6、IL-1?、IL-12p70、IL-10、IL-4、IFN-?、IL-2和IL-5)的动态变化水平,研究AD模型小鼠(APP/PS1)天然免疫调控与AD小鼠月龄增长之间变化的动态规律。结果:在小鼠脑组织中,随着小鼠年龄的增加(3 w、6 w、10 w、16 w、20 w和24 w),小胶质细胞炎症因子呈现一定的极化趋势。并且,与野生型相比,APP/PS1小鼠炎症因子TNF-?、IL-6、IL-1?呈现相反的变化趋势。检测10 w-16 w时段TNF-?,两组间差异显著(p<0.05)。10 w以上,与野生型(WT)相比,转基因(APP)组IFN-?上升明显(p<0.05)结论:综上,AD早期存在了增龄相关的小胶质细胞的活化,其机制值得进一步研究。

Objective Innateimmune dysfunction may be one of the keymechanisms leading to Alzheimer’s disease(AD).The aim of this study was to investigate the dynamic level of early polarization disorder in microglia of AD mice.Methods In this study,the dynamic changes of a variety of cytokines(TNF-?、IL-6、IL-1?、IL-12 p70、IL-10、IL-4、IFN-?、IL-2 and IL-5),which are related to the activation of microglia in AD double transgenic mice APPswe/PS1?E9(APP/PS1)were detected by Meso Scale Discovery(MSD).Furthermore,the dynamic law of changes between the innate immune regulation of AD model mice(APP/PS1)and AD mice ages were studied.Results Microglia inflammatory factors showed a certain polarization trend in mice brain tissuesas the age increases(3 w,6 w,10 w,16 w,20 w and 24 w).Moreover,compared with the wild type,the inflammatory factors TNF-?,IL-6,IL-1?of APP/PS1 mice showed opposite trends.TNF-?was measured during the 10 w-16 w period,and the difference between the two groups was significant(p<0.05).Compared with WT,IFN-?increased significantly(p<0.05)in the group of over 10 w mice.Conclusions In summary,there is an activation of age-related microglia in AD,and its mechanism deserves further study.