中国神经再生研究(英文版)

中国神经再生研究(英文版) ›› 2026, Vol. 21 ›› Issue (2): 466-477.doi: 10.4103/NRR.NRR-D-24-00777

• 综述:脑损伤修复保护与再生 • 上一篇    下一篇

色氨酸代谢与缺血性脑卒中：错综复杂的平衡

  

  • 出版日期:2026-02-15 发布日期:2025-05-20

Tryptophan metabolism and ischemic stroke: An intricate balance

Chongjie Yao1, 2, #, Dong Xie1, #, Yuchen Zhang1, 2, Yuanhao Shen2 , Pingping Sun3 , Zhao Ma1 , Jin Li1 , Jiming Tao1, *, Min Fang1, 4, *   

  1. 1 Rehabilitation Department, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China;  2 School of Acupuncture-Moxibustion and Tuina, Shanghai University of Traditional Chinese Medicine, Shanghai, China;  3 School of Rehabilitation Science, Shanghai University of Traditional Chinese Medicine, Shanghai, China;  4 Research Institute of Tuina, Shanghai Academy of Traditional Chinese Medicine, Shanghai, China
  • Online:2026-02-15 Published:2025-05-20
  • Contact: Min Fang, PhD, fm-tn0510@shutcm.edu.cn; Jiming Tao, PhD, taoyecheng@163.com.
  • Supported by:
    This work was supported by Shanghai Shenkang Center Demonstration Research Ward Construction, No. SHDC2022CRW010 (to MF); Shanghai Shenkang Center Medical Enterprise Integration and Innovation Collaborative Special Project, No. SHDC2022CRT018 (to MF); Shanghai Health System Key Supported Discipline-Rehabilitation Medicine, No. 2023ZDFC0301 (to JT); Science and Technology Development Project of Shanghai University of Traditional Chinese Medicine, No. 23KFL009 (to JT); Shanghai Postdoctoral Excellence Program, No. 2022515 (to CY); Yangfan Special Project of Shanghai Science and Technology Innovation Action Plan, No. 23YF1447600 (to CY); and China Postdoctoral Science Foundation, No. 2023M732338 (to CY).

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摘要：

缺血性脑卒中是一种以缺氧缺血为特征的病理状态，会引发一系列损伤反应。这些反应包括神经毒性、炎症、氧化应激、血脑屏障破坏和神经元死亡。在缺血性脑卒中中犬尿氨酸和5-羟色胺通路合成的色氨酸代谢物和酶表现出双重功能，这种神经毒性和神经保护之间的微妙平衡对于缺血性脑卒中的进展至关重要。犬尿氨酸等神经保护代谢物可通过多种机制发挥作用。例如，犬尿氨酸可竞争性阻断N-甲基-D-天冬氨酸受体，调节α7烟碱乙酰胆碱受体，并清除活性氧。而喹啉酸等神经毒性物质则会阻碍血管葡萄糖转运蛋白的发育，诱导活性氧介导的神经毒性，并破坏线粒体功能。此外，参与色氨酸代谢的酶也起着重要的作用。例如，犬尿氨酸通路中的吲哚胺2,3-双加氧酶和5-羟色胺通路中的色氨酸羟化酶可影响神经炎症和脑稳态。因此，色氨酸代谢产生的物质对缺血性脑卒中的发展有显著影响。脑卒中的治疗旨在恢复各种代谢物的平衡，但精确调节中枢神经系统内的色氨酸代谢仍然是治疗的挑战。因此，此次综述旨在阐明缺血性脑卒中中色氨酸代谢物和酶之间的复杂相互作用，以及开发对应的靶向疗法以恢复神经毒性和神经保护之间的微妙平衡。

关键词: 色氨酸代谢, 缺血性脑卒中, 脑卒中后认知障碍, 脑卒中后抑郁, 脑缺血, 神经保护, 神经毒性, 犬尿氨酸, 5-羟色胺, 血清素

Abstract: Ischemic stroke, which is characterized by hypoxia and ischemia, triggers a cascade of injury responses, including neurotoxicity, inflammation, oxidative stress, disruption of the blood–brain barrier, and neuronal death. In this context, tryptophan metabolites and enzymes, which are synthesized through the kynurenine and 5-hydroxytryptamine pathways, play dual roles. The delicate balance between neurotoxic and neuroprotective substances is a crucial factor influencing the progression of ischemic stroke. Neuroprotective metabolites, such as kynurenic acid, exert their effects through various mechanisms, including competitive blockade of N-methyl-D-aspartate receptors, modulation of α7 nicotinic acetylcholine receptors, and scavenging of reactive oxygen species. In contrast, neurotoxic substances such as quinolinic acid can hinder the development of vascular glucose transporter proteins, induce neurotoxicity mediated by reactive oxygen species, and disrupt mitochondrial function. Additionally, the enzymes involved in tryptophan metabolism play major roles in these processes. Indoleamine 2,3-dioxygenase in the kynurenine pathway and tryptophan hydroxylase in the 5-hydroxytryptamine pathway influence neuroinflammation and brain homeostasis. Consequently, the metabolites generated through tryptophan metabolism have substantial effects on the development and progression of ischemic stroke. Stroke treatment aims to restore the balance of various metabolite levels; however, precise regulation of tryptophan metabolism within the central nervous system remains a major challenge for the treatment of ischemic stroke. Therefore, this review aimed to elucidate the complex interactions between tryptophan metabolites and enzymes in ischemic stroke and develop targeted therapies that can restore the delicate balance between neurotoxicity and neuroprotection.

Key words: 5-hydroxytryptamine, cerebral ischemia, ischemic stroke, kynurenine, neuroprotection, neurotoxicity, post-stroke cognitive impairment, post-stroke depression, serotonin, tryptophan metabolism