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高同型半胱氨酸血症驱动的缺血性中风：揭示分子机制与治疗前景

Hyperhomocysteinemia-Driven Ischemic Stroke: Unraveling Molecular Mechanisms and Therapeutic Horizons.

作者信息

Li Bin, Kou Yushun, Zhang Lingna, Yi Lin

机构信息

School of Traditional Chinese and Western Medicine Gansu University of Chinese Medicine Lanzhou China.

出版信息

Food Sci Nutr. 2025 Jul 3;13(7):e70517. doi: 10.1002/fsn3.70517. eCollection 2025 Jul.

DOI:10.1002/fsn3.70517
PMID:40612136
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12224059/
Abstract

Homocysteine is a toxic intermediate in the metabolism of methionine, and impaired homocysteine metabolism can lead to hyperhomocysteinemia, whose clinical relevance to ischemic stroke has been confirmed by many studies and is considered an independent risk factor for ischemic stroke. This article reviews and analyzes studies related to ischemic stroke due to hyperhomocysteinemia. Firstly, the mechanism of hyperhomocysteinemia was examined, and it was clarified that hyperhomocysteinemia is the result of mutations in the genes of key enzymes involved in homocysteine metabolism or nutritional disorders of cofactors involved in homocysteine metabolism. Secondly, we reviewed that hyperhomocysteinemia may lead to a series of pathological processes such as vascular injury, thrombosis, and vasoconstriction through the mechanisms of inflammation and oxidative stress, neurotoxicity, and epigenetic dysregulation, which ultimately lead to the development of ischemic stroke. The article also provides a review of research on the prevention and treatment of ischemic stroke associated with hyperhomocysteinemia, specifically describing three large clinical vitamin supplementation trials, which, despite the heterogeneity of findings, provide partial evidence for prevention. This review will provide some insights and thoughts for studying the biological mechanisms of hyperhomocysteinemia-associated ischemic stroke and exploring novel therapies for its prevention and treatment.

摘要

同型半胱氨酸是甲硫氨酸代谢中的一种毒性中间产物，同型半胱氨酸代谢受损会导致高同型半胱氨酸血症，许多研究已证实其与缺血性中风的临床相关性，并且它被认为是缺血性中风的一个独立危险因素。本文回顾并分析了与高同型半胱氨酸血症所致缺血性中风相关的研究。首先，研究了高同型半胱氨酸血症的机制，明确其是同型半胱氨酸代谢关键酶基因突变或同型半胱氨酸代谢相关辅助因子营养紊乱的结果。其次，我们回顾了高同型半胱氨酸血症可能通过炎症和氧化应激、神经毒性及表观遗传失调机制导致一系列病理过程，如血管损伤、血栓形成和血管收缩，最终导致缺血性中风的发生。本文还综述了与高同型半胱氨酸血症相关的缺血性中风预防和治疗的研究，特别描述了三项大型临床维生素补充试验，尽管研究结果存在异质性，但为预防提供了部分证据。这篇综述将为研究高同型半胱氨酸血症相关缺血性中风的生物学机制以及探索其预防和治疗的新疗法提供一些见解和思路。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ca4a/12224059/eed736dbb0e7/FSN3-13-e70517-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ca4a/12224059/776177da42a2/FSN3-13-e70517-g005.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ca4a/12224059/776177da42a2/FSN3-13-e70517-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ca4a/12224059/dfdfeb987571/FSN3-13-e70517-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ca4a/12224059/2b48cc6e55dd/FSN3-13-e70517-g006.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ca4a/12224059/eed736dbb0e7/FSN3-13-e70517-g001.jpg

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本文引用的文献

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Efficacy of different traditional Chinese medicine decoctions in the treatment of ischemic stroke: a network meta-analysis.不同中药汤剂治疗缺血性中风的疗效：一项网状Meta分析
Front Pharmacol. 2024 Nov 1;15:1486458. doi: 10.3389/fphar.2024.1486458. eCollection 2024.
2
Homocysteine thiolactone and other sulfur-containing amino acid metabolites are associated with fibrin clot properties and the risk of ischemic stroke.同型半胱氨酸硫内酯和其他含硫氨基酸代谢物与纤维蛋白凝块特性和缺血性中风风险相关。
Sci Rep. 2024 May 16;14(1):11222. doi: 10.1038/s41598-024-60706-2.
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Engineering Redox Cofactor Balance for Improved 5-Methyltetrahydrofolate Production in .
工程化氧化还原辅助因子平衡以提高. 中 5-甲基四氢叶酸的产量。
J Agric Food Chem. 2024 May 1;72(17):9974-9983. doi: 10.1021/acs.jafc.4c00821. Epub 2024 Apr 16.
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Cerebrolysin for acute ischaemic stroke.脑活素治疗急性缺血性脑卒中。
Cochrane Database Syst Rev. 2023 Oct 11;10(10):CD007026. doi: 10.1002/14651858.CD007026.pub7.
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Homocysteine Reduction for Stroke Prevention: Regarding the Recent AHA/ASA 2021 Prevention of Stroke in Patients With Stroke and Transient Ischemic Attack.降低同型半胱氨酸以预防中风：关于美国心脏协会/美国中风协会2021年最新发布的中风和短暂性脑缺血发作患者的中风预防指南
Pharmgenomics Pers Med. 2023 Oct 3;16:895-900. doi: 10.2147/PGPM.S426421. eCollection 2023.
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Low vitamin B levels may predict the risk of ischemic stroke: A cross-sectional study.低维生素 B 水平可能预示缺血性中风的风险：一项横断面研究。
J Clin Neurosci. 2023 Nov;117:125-135. doi: 10.1016/j.jocn.2023.09.024. Epub 2023 Oct 5.
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Association of Homocysteine with Acute Stroke and Its Subtypes in the Chinese Population.中国人群中同型半胱氨酸与急性脑卒中及其亚型的关联。
Neuropsychiatr Dis Treat. 2023 Jun 15;19:1435-1442. doi: 10.2147/NDT.S409591. eCollection 2023.
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Ischaemic stroke with multi-focal venous and arterial thrombosis due to hyperhomocysteinemia: anabolic androgenic steroid use and MTHFR c.667 C > T variant - a case report.由于高同型半胱氨酸血症导致的缺血性中风伴多灶性静脉和动脉血栓形成：使用合成代谢雄激素类固醇和 MTHFR c.667C > T 变体 - 病例报告。
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A machine learning model for visualization and dynamic clinical prediction of stroke recurrence in acute ischemic stroke patients: A real-world retrospective study.急性缺血性卒中患者卒中复发可视化及动态临床预测的机器学习模型：一项真实世界回顾性研究。
Front Neurosci. 2023 Mar 27;17:1130831. doi: 10.3389/fnins.2023.1130831. eCollection 2023.
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Dietary vitamin B12 deficiency impairs motor function and changes neuronal survival and choline metabolism after ischemic stroke in middle-aged male and female mice.饮食性维生素 B12 缺乏症可损害中年雄性和雌性小鼠缺血性脑卒中后的运动功能，并改变神经元存活和胆碱代谢。
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