载脂蛋白E基因与缺血性卒中后脑损伤关系的研究进展

doi:10.3969/j.issn.1673-5765.2026.05.007

摘要/Abstract

摘要： 载脂蛋白E（apolipoprotein E，APOE）基因及其编码蛋白ApoE是缺血性卒中脑细胞保护研究中值得关注的靶点。ApoE蛋白参与体内脂质转运、胶质细胞和神经元支持、炎症反应调节，以及神经血管单元和血脑屏障稳态维持等与脑组织损伤和修复密切相关的病理生理过程。临床前实验提示，Apoe基因缺失小鼠模型中，内源性ApoE蛋白缺乏可加重缺血性脑损伤；在人源化APOE2、APOE3和APOE4基因敲入小鼠模型中，表达人类ApoE4蛋白亚型的小鼠具有更严重的脑梗死和神经功能缺损表现。另外，干预性实验证明，ApoE模拟肽CN-105和COG1410在缺血性卒中动物模型中具有调节炎症反应、维持血脑屏障稳定性及改善神经功能的作用。临床研究显示，APOE基因型与缺血性卒中的发生风险、发病年龄、短期功能结局及卒中后认知结局的关系尚无统一结论。APOE基因目前尚不足以成为缺血性卒中的独立预测指标或成熟的干预靶点。本文围绕APOE基因及ApoE蛋白相关通路在缺血性卒中后脑损伤中的作用，综述其可能机制、临床前实验和临床研究证据，以及针对该通路的治疗探索。

文章导读： 本文对载脂蛋白E基因及其编码蛋白在缺血性卒中脑损伤病理过程中的作用进行了综述，重点关注其临床前实验结果向临床转化的可能性和目前研究的局限性，并提出了后续研究应重点关注的方向。

关键词: 缺血性卒中; 载脂蛋白E; 基因; 蛋白; 脑细胞保护

Abstract: The apolipoprotein E (APOE) gene and its encoded protein ApoE represent promising targets worthy of attention in studies of brain cytoprotection for ischemic stroke. The ApoE protein is involved in pathophysiological processes closely linked to tissue injury and repair after cerebral ischemia, including cerebral lipid transport, glia-neuron support, regulation of inflammatory responses, and maintenance of the neurovascular unit and the blood-brain barrier homeostasis. Preclinical studies have demonstrated that endogenous ApoE deficiency in Apoe gene knockout mice aggravates experimental ischemic brain injury. Humanized APOE2, APOE3, and APOE4 knock-in mouse models further indicate that mice expressing the human ApoE4 protein isoform may develop more severe cerebral infarction and neurological deficits. In addition, interventional studies have verified that ApoE mimetic peptides CN-105 and COG1410 exert effects of regulating inflammatory responses, stabilizing the blood-brain barrier, and improving neurological function in animal models of ischemic stroke. Clinical studies have yielded inconsistent findings regarding the associations between APOE genotype and ischemic stroke risk, age at onset, short-term functional outcomes, and post-stroke cognitive outcomes. Current evidence is insufficient to support APOE genotype as an independent predictive biomarker or a well-established therapeutic target for ischemic stroke. This review summarizes the potential mechanisms, preclinical and clinical research evidence regarding the APOE gene and ApoE protein-related pathways in post-ischemic brain injury, as well as therapeutic strategies targeting ApoE-associated pathways.

Key words: Ischemic stroke; Apolipoprotein E; Gene; Protein; Brain cytoprotection

中图分类号:

常曹文静, 许淑红, 李俭, 李姝雅. 载脂蛋白E基因与缺血性卒中后脑损伤关系的研究进展[J]. 中国卒中杂志, 2026, 21(5): 570-576.

CHANG-CAO Wenjing, XU Shuhong, LI Jian, LI Shuya. Research Progress on the Relationship between the Apolipoprotein E Gene and Brain Injury after Ischemic Stroke [J]. Chinese Journal of Stroke, 2026, 21(5): 570-576.

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链接本文: https://www.chinastroke.org.cn/CN/10.3969/j.issn.1673-5765.2026.05.007

https://www.chinastroke.org.cn/CN/Y2026/V21/I5/570

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