靶向肝脏改善轻度认知障碍的作用机制与治疗策略

李金玉; 姜恒; 冯对平; 聂继盛

doi:10.12449/JCH260838

靶向肝脏改善轻度认知障碍的作用机制与治疗策略

DOI: 10.12449/JCH260838

李金玉^{1, 2},
姜恒³,
冯对平²,
聂继盛^3, , ,

1.
山西医科大学法医学院，太原 030001
2.
山西医科大学第一医院肿瘤与血管介入科，太原 030001
3.
山西医科大学公共卫生学院，煤炭环境致病与防治教育部重点实验室，太原 030001

基金项目:

国家自然科学基金 (82200650);

山西省自然科学基金 (202203021212046)

利益冲突声明：本文不存在任何利益冲突。

作者贡献声明：李金玉负责设计论文框架，起草论文；姜恒参与论文修改，绘制图表；冯对平参与查阅相关文献，修改论文；聂继盛负责拟定写作思路，指导撰写文章并最后定稿。

详细信息

通信作者:
聂继盛， niejisheng@sxmu.edu.cn （ORCID： 0000-0003-4351-2017）

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出版历程
- 收稿日期: 2025-12-26
- 录用日期: 2026-03-05
- 出版日期: 2026-08-25

Liver-targeted therapies for improving mild cognitive impairment: Mechanism of action and treatment strategies

Jinyu Li^{1, 2},
Heng Jiang³,
Duiping Feng²,
Jisheng Nie^{3
, ,
,}

1.
School of Forensic Medicine，Shanxi Medical University，Taiyuan 030001，China
2.
Department of Oncology and Vascular Intervention，The First Hospital of Shanxi Medical University，Taiyuan 030001，China
3.
School of Public Health，MOE Key Laboratory of Coal Environmental Pathogenicity and Prevention，Shanxi Medical University，Taiyuan 030001，China

Research funding:

National Natural Science Foundation of China (82200650);

Natural Science Foundation of Shanxi Province (202203021212046)

More Information

Corresponding author: Nie Jisheng， niejisheng@sxmu.edu.cn （ORCID： 0000-0003-4351-2017）

摘要

摘要: 轻度认知障碍（MCI）是阿尔茨海默病的重要前驱阶段，其发生与肝脏功能密切相关。肝脏作为代谢器官，通过肝-脑轴调控认知功能。流行病学提示肝功能指标与MCI存在关联。肝脏通过过氧化物酶体增殖物激活受体α-低密度脂蛋白受体相关蛋白质1通路清除外周β-淀粉样蛋白；分泌成纤维细胞生长因子21、可溶性环氧化物水解酶等肝因子调节神经元能量代谢；介导氧化应激与系统性炎症反应等途径影响认知功能。抗炎/抗氧化、饮食模式调整、有氧运动是调节肝脏降低MCI发生的有效措施。本综述系统阐述肝-脑轴在MCI中的作用和机制，为开发基于肝脏靶点的认知障碍治疗提供新视角。
- 认知功能障碍 /
- 肝-脑轴 /
- 治疗学
Abstract: Mild cognitive impairment （MCI） is a critical precursor stage of Alzheimer’s disease， and the development of MCI is closely associated with liver function. As a core metabolic organ， the liver regulates cognitive function through the liver-brain axis. Epidemiological studies have shown the association between liver function parameters and MCI. The liver affects cognitive function by clearing peripheral β-amyloid （mainly via the PPARα-LRP-1 pathway）， secreting hepatic factors such as FGF21 and sEH to modulate neuronal energy metabolism， and mediating oxidative stress and systemic inflammatory responses. Anti-inflammatory/antioxidant measures， dietary pattern adjustments， and aerobic exercise are currently effective strategies for regulating liver function and mitigating mild cognitive impairment. This article systematically reviews the role and mechanism of the liver-brain axis in MCI， in order to provide new perspectives for developing liver-targeted therapies for cognitive impairment.
- Cognitive Dysfunction /
- Liver-Brain Axis /
- Therapeutics

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注： Aβ，β-淀粉样蛋白；PPARα，过氧化物酶体增殖物激活受体α；FGF21，成纤维细胞生长因子21；sEH，可溶性环氧化物水解酶；SELENOP，硒蛋白P；MANF，中脑星形胶质细胞源性神经营养因子；LRP-1，低密度脂蛋白受体相关蛋白质1；IL-6，白细胞介素6；TNF-α，肿瘤坏死因子α；CRP，C反应蛋白；ROS，活性氧；LPS，脂多糖。

图 1 肝损伤致认知障碍机制示意图

Figure 1. Schematic illustration of the mechanism underlying liver injury-induced cognitive impairment

下载: 全尺寸图片幻灯片

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