| APP/PS1双转基因小鼠的认知功能、炎症与肠道菌群特征分析 |
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| 引用本文： | 王一媚,张瑜杰,彭晨芮,李金星,程如越,沈曦,何方.APP/PS1双转基因小鼠的认知功能、炎症与肠道菌群特征分析[J].现代预防医学,2022,0(23):4379-4384. |
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| 作者姓名： | 王一媚 张瑜杰 彭晨芮 李金星 程如越 沈曦 何方 |
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| 作者单位： | 四川大学华西公共卫生学院/四川大学华西第四医院，四川 成都 610041 |
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| 摘 要： | 目的 探究阿尔茨海默症动物模型APP/PS1双转基因小鼠的认知功能、炎症及肠道菌群特征。方法 15只3月龄WT雄性小鼠为对照组，15只3月龄APP/PS1双转基因小鼠为模型组，饲养6个月后进行水迷宫实验，观察潜伏期。实验结束后采集小鼠血清、海马组织和粪便，测定小鼠血清细胞因子、海马Aβ蛋白沉积和细胞因子表达情况以及肠道菌群多样性和群落结构。结果 APP/PS1组小鼠海马中有明显的Aβ蛋白沉积、水迷宫潜伏期显著增加(t=-2.16；t=-3.20，P<0.05)。WT组小鼠血清LPS水平显著高于APP/PS1组(t=2.97，P<0.01)，IL-1β水平显著低于APP/PS1组(t=-3.69，P<0.01)。APP/PS1组小鼠海马组织中BDNF mRNA表达水平显著高于WT组(Z=-2.79，P<0.01)。APP/PS1双转基因小鼠的肠道菌群Alpha多样性显著低于WT组(t=3.01，P<0.05)，Beta多样性分析表明两组群落结构具有显著差异(R=0.45，P<0.05)；APP/PS1组的疣微菌门和阿克曼氏菌属的相对丰度显著低于WT组(Z=2.61，P<0.05)。结论 APP/PS1组出现明显的认知功能下降、炎症反应以及肠道菌群结构的异常改变。肠道菌群可能是防治阿尔茨海默症的新靶点，值得进一步研究。
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| 关 键 词： | APP/PS1 阿尔茨海默症 认知功能 炎症反应 肠道菌群 |
Cognitive function,inflammation and gutmicrobiota in APP/PS1 mice |
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| WANG Yi-mei,ZHANG Yu-jie,PENG Chen-rui,LI Jin-xing,CHENG Ru-yue,SHEN Xi,HE Fang.Cognitive function,inflammation and gutmicrobiota in APP/PS1 mice[J].Modern Preventive Medicine,2022,0(23):4379-4384. |
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| Authors: | WANG Yi-mei ZHANG Yu-jie PENG Chen-rui LI Jin-xing CHENG Ru-yue SHEN Xi HE Fang |
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| Affiliation: | West China School of Public Health and West China Fourth Hospital, Sichuan Uniersity, Chengdu, Sichuan 610041, China |
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| Abstract: | Objective To investigate the alteration of immune system, inflammation, cognitive function, structure of gut microbiota in APP/PS1 mice with Alzheimer ’s disease. Methods WT 3 month year-old mice were used as the WT group (n=15), and APP/PS1 3 month year-old mice were used as the APP/PS1 group (n=15). Morris water maze test was performed at 6 months of feeding to observe the latency of water maze. After the experiment, the serum, hippocampus, organs and feces of mice were collected and measured for serum cytokines, Aβ protein, Alpha diversity, Beta diversity and relative abundance of gut microbiota, respectively. Results Aβ protein deposition and water maze latency increased significantly in APP/PS1 mice (t=-2.16; t=-3.20, P<0.05). LPS level in WT group was significantly higher than that in APP/PS1 group (t=2.97, P<0.01). IL-1β level in WT group was significantly lower than that in APP/PS1 group (t=-3.69, P<0.01). The relative expression levels of BDNF mRNA in the hippocampus of the APP/PS1 group were significantly higher than that of WT group (Z=-2.79, P<0.01). Alpha diversity of the APP/PS1 was significantly lower than that of WT group (t=3.01, P<0.05). Beta diversity of gut analysis showed that there was significant difference in community structure between groups (R=0.45, P<0.05). Verrucomicrobiota and Akkermansia in the APP/PS1 group was lower than that in the WT group (Z=2.61, P<0.05). Conclusion APP/PS1 mice have cognitive decline, abnormal changes in inflammatory response and gut microbiota structure. Gut microbiota may be a new target for prevention and treatment of Alzheimer’ s disease. |
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| Keywords: | APP/PS1 Alzheimer’s disease Cognitive function Inflammatory response Gut microbiota |
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