摘要： 目的 探讨长时间大量饮用不同乙醇含量的饮料对小鼠海马内参与自噬的哺乳动物雷帕霉素靶蛋白（mTOR）及c-JunN末端激酶（JNK）通路的影响，揭示含乙醇饮料对认知功能的影响及机制。方法 将40只成年雌性小鼠随机分为对照（蒸馏水）组及不同浓度（2.5% vol、11% vol及52% vol）乙醇组。利用Morris水迷宫检测小鼠认知功能，通过HE染色观察小鼠锥体细胞形态变化，用免疫印迹及免疫荧光法检测小鼠海马内相关蛋白的表达情况。结果 2.5% vol、52% vol乙醇组小鼠出现认知障碍。2.5% vol、52% vol乙醇组小鼠mTOR-4EBP1通路相关蛋白表达高于对照组（P<0.05），自噬及JNK通路相关蛋白表达低于对照组（P<0.05）。11% vol乙醇组p-4EBP1表达低于2.5% vol、52% vol乙醇组（P<0.05），p-JNK及Beclin1蛋白表达高于2.5% vol、52% vol乙醇组（P<0.01）。结论 长期过量饮用含2.5% vol、52% vol乙醇饮料对小鼠认知功能的损害比含11% vol乙醇的饮料更重，海马内与mTOR和JNK通路相关的自噬抑制可能参与此过程。

酒精饮料对小鼠认知功能的影响及其机制

边欢欢¹, 程美嘉², 吴仪¹, 李彦怡³, 邹丹⁴

1. 沈阳医学院基础医学院病理生理学教研室, 沈阳 110034;
2. 大阪大学大学院医学系研究科医学统计学教研室, 大阪 565-0871;
3. 沈阳医学院2018级临床医学专业, 沈阳 110034;
4. 沈阳医学院基础医学院免疫学教研室, 沈阳 110034

收稿日期:2022-06-12出版日期:2023-03-30发布日期:2023-03-21
通讯作者:邹丹E-mail:2306344641@qq.com
作者简介:边欢欢(1993-),女,硕士研究生.
基金资助:国家级大学生创新创业训练计划（202010164003）；辽宁省教育厅科学研究经费项目（SYYX202002）；沈阳医学院研究生科技创新基金（Y20210505）


关键词: 乙醇, 认知, 哺乳动物雷帕霉素靶蛋白, c-Jun N末端激酶, 自噬
Abstract: Objective To investigate the effects of long-term consumption of beverages with different ethanol content on mammalian target of rapamycin （mTOR） and c-Jun N-terminal kinase （JNK） pathways involved in autophagy in hippocampus of mice，and to reveal the mechanism of cognitive effects of alcohol-containing beverages. Methods Forty adult female mice were randomly divided into control （distilled water） and ethanol groups with different concentrations （2.5%vol，11%vol，and 52%vol）. The Morris water maze was used to detect the cognitive function of mice，and HE staining was used to observe the morphological changes in mouse pyramidal cells. Western blotting and immunofluorescence were used to detect the expression of related proteins in the hippocampus of mice. Results The mice in the 2.5%vol and 52%vol ethanol groups showed cognitive impairment. Protein expression of the mTOR-4EBP1 pathway in the 2.5%vol and 52%vol ethanol groups was higher （P<0.05），whereas that of the autophagy and JNK pathway was lower （P<0.05） than those in the control group. The expression of p-4EBP1 in the 11%vol ethanol group was lower than that in the 2.5%vol and 52%vol ethanol groups （P<0.05），and the expression of p-JNK and Beclin1 proteins was higher than those in the 2.5%vol and 52%vol ethanol groups （P<0.01）. Conclusion Long-term excessive consumption of beverages with 2.5%vol and 52%vol ethanol caused more cognitive impairment in mice than that with 11%vol ethanol. Autophagy inhibition related to the mTOR and JNK pathways in the hippocampus may be involved in this process.
Key words: alcohol, cognition, mammalian target of rapamycin, c-Jun N-terminal kinase, autophagy
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