中国神经再生研究(英文版) ›› 2026, Vol. 21 ›› Issue (8): 3588-3597.doi: 10.4103/NRR.NRR-D-24-01384

• 原著:脑损伤修复保护与再生 • 上一篇    下一篇

缺血性脑卒中的代谢组学研究:从基础研究到临床

  

  • 出版日期:2026-08-18 发布日期:2026-04-27

Advances in metabolomics of biomarkers for ischemic stroke: From bench to clinic

Jiaxin Sun1, #, Chenxin Xiao2, #, Jingyuan Zhang1, Feng Lin1, Yue Xu1, Yanyu Li1, Lei Zhang1, *, Wenli Chen3, 4, *   

  1. 1Department of Cerebrovascular Disease, The Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai, Guangdong Province, China; 
    2School of Pharmacy, Macau University of Science and Technology, Macao Special Administrative Region, China; 
    3Department of Pharmacy, The Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai, Guangdong Province, China; 
    4Guangdong-Hong Kong-Macao University Joint Laboratory of Interventional Medicine, the Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai, Guangdong Province, China
  • Online:2026-08-18 Published:2026-04-27
  • About author:Wenli Chen, MD, chenwenl@mail3.sysu.edu.cn; Lei Zhang, MD, zhangl92@sysu.edu.cn.
  • Supported by:
    This work was supported by the National Natural Science Foundation of China, No. 82104144 (to LZ); The Fifth Affiliated Hospital of Sun Yat-sen University of Outstanding Young Talents Cultivation Program, No. 3320104100322 (to WC); “Five Five” Young Talents Program, No. 220904094231 (to LZ); and the Guangdong-Hong Kong-Macao University Joint Laboratory of Interventional Medicine Foundation of Guangdong Province , No. 2023LSYS001 (to WC).

摘要:

代谢组学通过分析小分子代谢物的动态变化,为揭示缺血性脑卒中的兴奋性毒性、氧化应激、炎症等核心机制提供了新视角。然而,现有研究受限于样本异质性、技术差异及系统性不足,阻碍其临床转化。通过检索并筛选出2005年到2024年128篇文献,在大脑中动脉闭塞小鼠模型和大鼠模型中分别鉴定出125个和246个差异代谢物,而缺血性脑卒中患者中观察到具有显著变化的代谢物达764个。通过跨物种数据比较发现,谷氨酸和甘油在啮齿类动物与临床样本中均上调,LysoPC(18:0)则普遍下调,提示其作为跨物种生物标志物的潜力。代谢通路分析进一步显示,三羧酸循环、甘油磷脂代谢等通路在缺血性脑卒中发生显著紊乱,且大鼠模型的代谢特征更接近临床患者,提示其作为转化研究模型的优势。此外,研究明确了代谢物与核心病理机制的关联,如谷氨酸升高加剧神经元钙超载,乳酸堆积与氧化应激相关,LysoPC(18:0)的下调反映了炎症级联反应,为机制靶向治疗提供了方向。基于研究结果,亚油酸(LA)水平降低可作为缺血性脑卒中风险预测指标,而同型半胱氨酸与动脉粥样硬化性缺血性脑卒中亚型(LAA)的关联为分型诊断提供了依据。血糖和谷氨酸的动态变化与出血转化及不良预后相关,提示其在病程监测中的价值。此研究通过整合多模型数据筛选出了普适性的生物标志物,为缺血性脑卒中的临床诊断和治疗提供了新的靶点。


https://orcid.org/0000-0002-3094-2766 (Wenli Chen); 

https://orcid.org/0000-0001-7534-3647 (Lei Zhang)

关键词: 生物标记物, 缺血性脑卒中, 代谢组学, 患者, 啮齿动物

Abstract: Ischemic stroke, a neurological impairment caused by cerebral vascular occlusion, accounts for 87% of the cases of stroke. Recent studies have shown that changes in the abundance of metabolites can directly reveal the cellular phenotypes and identify the clinical implications of stroke diagnosis and therapy. However, systematic research to clarify the relationship between biomarkers and the mechanisms of ischemic stroke remains limited. In this study, we reviewed articles on ischemic stroke metabolites from 2005 to 2024, identified metabolites showing significant changes, and constructed a metabolite database based on the findings from 128 studies. The database included 125 differential metabolites detected in a middle cerebral artery occlusion mouse model, 246 detected in an middle cerebral artery occlusion rat model, and 764 identified in ischemic stroke patient samples. Differential metabolites from various samples were then screened and classified into positive and negative categories based on their correlation with stroke prognoses. Based on this analysis, three positive metabolites and two negative metabolites were identified. Glutamic acid, glycerol, and 1-octadecanoyl-sn-glycero-3-phosphocholine (LysoPC(18:0)) were further recognized as potential biomarkers. Imbalances in metabolic pathways such as alanine, aspartate, and glutamate metabolism as well as the citrate cycle (tricarboxylic acid cycle) were analyzed. These imbalances may influence the pathogenesis of ischemic stroke by altering biological processes such as excitotoxicity, oxidative stress, inflammation, and energy metabolism. The identification and analysis of these potential biomarkers may provide valuable targets and strategies for prediction, diagnosis, and prognostic assessment of ischemic stroke.

Key words: biomarker, energy metabolism, excitotoxicity, glutamic acid, glycerol, ischemic stroke, metabolomics, oxidative stress, patient, rodent