[1]韩洁玢,孙淮庆,王佩佩,等.地中海饮食通过调控肝脏X受体改善阿尔茨海默病小鼠认知功能[J].陕西医学杂志,2025,54(7):873-881,893.[doi:DOI:10.3969/j.issn.1000-7377.2025.07.002]
　HAN Jiebin,SUN Huaiqing,WANG Peipei,et al.The Mediterranean diet improves cognitive function in Alzheimer’s disease mice by regulating liver X receptors[J].,2025,54(7):873-881,893.[doi:DOI:10.3969/j.issn.1000-7377.2025.07.002]
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地中海饮食通过调控肝脏X受体改善阿尔茨海默病小鼠认知功能

《陕西医学杂志》[ISSN:1000-7377/CN:61-1281/TN]

卷:
54
期数:
2025年7期
页码:
873-881,893
栏目:
基础研究
出版日期:
2025-07-05

文章信息/Info

Title:
The Mediterranean diet improves cognitive function in Alzheimer’s disease mice by regulating liver X receptors
作者:
韩洁玢1; 孙淮庆2; 王佩佩1; 董粤蓉1; 吴婷2; 何清1
（1.徐州医科大学附属徐州市立医院，江苏 徐州 221000；2.南京医科大学南京第一附属医院，江苏 南京 210029）
Author(s):
HAN Jiebin1; SUN Huaiqing2; WANG Peipei1; DONG Yuerong1; WU Ting2; HE Qing1
(1.Department of Neurology，The Affiliated Xuzhou Municipal Hospital of Xuzhou Medical University，Xuzhou 221000，China；2.Department of Neurology，the First Affiliated Hospital of Nanjing Medical University,Nanjing 210029,China)
关键词:
地中海饮食; 阿尔茨海默病; 认知功能障碍; 肝脏X受体; 神经炎症; 5xFAD小鼠
Keywords:
Mediterranean diet; Alzheimer’s disease; Cognitive dysfunction; Liver X receptors; Neuroinflammation; 5xFAD mice
分类号:
R 742
DOI:
DOI:10.3969/j.issn.1000-7377.2025.07.002
文献标志码:
A
摘要:
目的：探讨地中海饮食（MD）对小鼠认知功能、突触功能、神经炎症及Aβ沉积的改善作用及其潜在机制。方法：C57BL/6小鼠10只作为对照组，5xFAD小鼠20只随机分为5xFAD组和5xFAD-MD组，每组各10只，对5xFAD-MD组小鼠进行8周MD干预，对照组和5xFAD组小鼠每天给予普通饲料饲养。通过Y迷宫、新物体识别和巴恩斯迷宫测试评估小鼠认知功能，采用免疫印迹检测突触相关蛋白突触后致密蛋白95（PSD95）和突触蛋白1（SYN-1）表达量，利用硫磺素-S染色、免疫荧光及免疫印迹评估海马Aβ沉积水平，免疫荧光检测海马小胶质细胞肝脏X受体（LXR）的激活情况。结果：与对照组比较，5xFAD小鼠体型小、毛发毛躁稀疏，体重增长下降；进入新异臂的时间百分比、进入新异臂的次数及新物体识别测试阶段接触新换物体侧的时间百分比显著下降（均P＜0.05）、测试期小鼠找到迷宫目标区域时间延长（P＜0.05），Aβ蛋白表达水平、小胶质细胞数量显著增加（均P＜0.05），小鼠脑内LXR荧光强度降低，PSD95、SYN-1的表达减少（均P＜0.05）；与5xFAD组比较，5xFAD-MD组小鼠体型大、毛发浓密、体重增长，进入新异臂的时间百分比、新物体识别测试阶段接触新换物体侧的时间百分比增加（均P＜0.05）、测试期小鼠找到迷宫目标区域时间缩短（P＜0.05），Aβ蛋白表达水平、小胶质细胞数量显著下降（均P＜0.05），小鼠脑内LXR荧光强度增加，PSD95、SYN-1的表达增加（均P＜0.05）。结论：MD通过改善突触功能和抑制神经炎症，发挥对5xFAD小鼠的认知保护作用，其机制可能与激活LXR并抑制小胶质细胞活化有关。
Abstract:
Objective:This study aimed to investigate the effects of the Mediterranean Diet(MD) on cognitive function，synaptic function，neuroinflammation，and Aβ deposition in 5xFAD mice，and to explore the potential underlying mechanisms.Methods：Ten C57BL/6 mice were used as the control group，and 20 5xFAD mice were randomly divided into the 5xFAD group and the 5xFAD-MD group，with 10 mice in each group.The 5xFAD-MD group mice were subjected to an 8-week MD intervention，while the control group and the 5xFAD group mice were fed normal chow daily.The cognitive function of the mice was evaluated by Y-maze，novel object recognition and Barnes maze tests.The expression levels of synaptic-related proteins PSD95 and SYN-1 were detected by Western blotting.The Aβ deposition level in the hippocampus was evaluated by Thioflavin-S staining，immunofluorescence and Western blotting.The activation of LXR receptor in hippocampal microglia was detected by immunofluorescence.Results:Compared with the control group，5xFAD mice were smaller in size，had rough and sparse fur，and showed a decreased weight gain.The percentage of time spent entering the novel arm and the percentage of time spent exploring the newly replaced object side in the novel object recognition test stage were significantly decreased(all P＜0.05)，and the time required for the mice to find the target area in the maze during the test period was prolonged(P＜0.05).The expression level of Aβ protein and the number of microglia were significantly increased(all P＜0.05)，while the fluorescence intensity of LXR in the mouse brain and the expression of PSD95 and SYN-1 were decreased(all P＜0.05).Compared with the 5xFAD group，5xFAD-MD group mice were larger in size，had thick fur，and gained weight.The percentage of time spent entering the novel arm, the number if ontvies into the novel arm,and the percentage of time spent exploring the newly replaced object side in the novel object recognition test stage，all increused(all P＜0.05).The time required for the mice to find the target area in the maze during the test period，was shortened(all P＜0.05).The expression level of Aβ protein and the number of microglia significantly decreased(all P＜0.05)，while the fluorescence intensity of LXR in the mouse brain and the expression of PSD95 and SYN-1 were increased(all P＜0.05).Conclusion:MD exerts cognitive protect effects in 5xFAD mice by ameliorating synaptic function and suppressing neuroinflammation，potentially via activation of LXR receptors and inhibition of microglial activation.

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备注/Memo

备注/Memo:
国家自然科学基金资助项目（81772454，81971237）；江苏省科技局科研项目（BE2017734）；江苏省重点研发计划重点项目（BE2023023-2）
更新日期/Last Update: 2025-07-07