低聚半乳糖对AD模型小鼠认知功能及炎性反应的调节作用  

EFFECTS OF GALACTO-OLIGOSACCHARIDE ON COGNITIVE FUNCTION AND INFLAMMATORY RESPONSE IN ALZHEIMER’S DISEASE MODEL MICE

作　　者：张静竹 陈艳秋 潘鹏宇 胡爽 安丽 ZHANG Jing-zhu;CHEN Yan-qiu;PAN Peng-yu;HU Shuan;AN Li(Department of Nutrition and Food Hygiene,School of Public Health,China Medical University,Shenyang 110122;Jinzhou Medical University,Jinzhou 121001,China)

机构地区：[1]中国医科大学公共卫生学院营养与食品卫生学教研室,沈阳110122 [2]锦州医科大学健康管理学院健康评估教研室,锦州121001

出　　处：《营养学报》2021年第4期377-383,共7页Acta Nutrimenta Sinica

基　　金：国家自然青年科学基金(No.81903308)。

摘　　要：目的探讨低聚半乳糖(GOS)改善阿尔茨海默病(AD)模型小鼠认知功能的作用及机制。方法将5月龄APPswe/PS1dE9双转基因小鼠分成AD模型组(AD组)和AD干预组(AD+GOS),将同窝出生野生型小鼠分成野生对照组(WT)和野生干预组(WT+GOS),每组10只。干预组喂饲含有5%GOS的饲料,WT和AD组喂饲普通饲料,连续干预6月。采用Morris水迷宫进行神经行为学检查,采用硫黄素T染色法检测脑组织Aβ沉积情况,采用qRT-PCR和Western Blotting法检测大脑皮质GFAP(反应性星形胶质细胞标记物)、CD86(小胶质细胞M1型活化标记物)以及Toll样受体-2(TLR2)、白介素-1β(IL-1β)mRNA和蛋白表达水平,Western Blotting法检测大脑皮质核转录因子(NF-κB)p65蛋白表达水平。结果与WT组相比,AD模型组小鼠逃避潜伏期增加,停留时间、穿台次数减少,脑组织Aβ沉积个数增多,GFAP、CD86、IL-1β、TLR2 mRNA和蛋白、NF-κBp65蛋白相对表达水平升高(P<0.05或P<0.01)。与AD组相比,AD+GOS组小鼠逃避潜伏期降低,停留时间、穿台次数增加,脑组织Aβ沉积个数减少,GFAP、CD86、IL-1β、TLR2mRNA和蛋白、NF-κBp65蛋白相对表达水平下降(P<0.05或P<0.01)。结论GOS可下调TLR2表达,降低反应性星形胶质细胞和小胶质细胞M1型活化,减少NF-κBp65活化和IL-1β表达,减轻Aβ沉积,改善AD模型小鼠的认知功能损伤。Objective To investigate the effects of galacto-oligosaccharide(GOS)on cognitive function in Alzheimer’s disease(AD)model mice.Methods At 5 months of age,APPswe/PS1 dE9 double-transgenic mice were assigned into AD and AD+GOS groups,and their wild-type(WT)littermates into WT and WT+GOS groups.Mice in WT+GOS and AD+GOS groups were fed a diet containing 5%GOS;mice in WT and AD groups received a normal pellet feed.The treatment was continued for 6 months,and the Morris water maze test was used for assessing spatial learning and memory at the end of the experiment.Aβdeposits in the brain tissue were detected by thioflavin T staining.The mRNA expression levels of GFAP,CD86,and TLR2,IL-1βin the cerebral cortex were tested using quantitative real-time polymerase chain reaction.The protein expression levels of GFAP,CD86,TLR2,NF-κBp65 and IL-1βin the cerebral cortex were detected using Western blotting.Results Compared with the wild control mice,the AD model mice had longer escape latency,shorter time stayed in the platform,higher number of Aβplaques in the brain and increased expression of GFAP,CD86,IL-1β,TLR2 mRNA and protein as well as NF-κBp65 protein in the cerebral cortex(P<0.01,P<0.05).Compared with AD model mice,the escape latency was shortened;the staying time and the times of cross platform were augmented;the numbers of Aβplaques were decreased in the brain;the relative expression levels of GFAP,CD86,IL-1β,TLR2 mRNA and protein as well as NF-κBp65 protein in the cerebral cortex were significantly reduced in the AD model mice treated with GOS(P<0.01,P<0.05).Conclusion GOS improves cognitive impairment and alleviates Aβdeposition in the brain in APPswe/PS1 dE9 double transgenic AD mice by inhibiting the expression of NF-κBp65 and IL-1β,which is mediated by the reduction of reactive astrocytes and M1 type microglia through down-regulated TLR2 expression.

关 键 词：阿尔茨海默病 Β-淀粉样蛋白 低聚半乳糖 胶质细胞 Toll样受体-2 

分 类 号：R151.2[医药卫生—营养与食品卫生学]