中国神经再生研究(英文版) ›› 2026, Vol. 21 ›› Issue (4): 1483-1496.doi: 10.4103/NRR.NRR-D-24-01404

• 综述:神经损伤修复保护与再生 • 上一篇    下一篇

细胞器交响曲:脑卒中病理生物学中的 NRF2 和 NF-κB

  

  • 出版日期:2026-04-15 发布日期:2025-07-26

Organelle symphony: Nuclear factor erythroid 2-related factor 2 and nuclear factor-kappa B in stroke pathobiology

Ziliang Hu1 , Mingyue Zhao1 , Hangyu Shen1 , Liangzhe Wei1 , Jie Sun1 , Xiang Gao1, 2, *, Yi Huang1, 2, *   

  1. 1 Department of Neurosurgery, Ningbo Key Laboratory of Nervous System and Brain Function, The First Affiliated Hospital of Ningbo University, Ningbo, Zhejiang Province, China;  2 Key Laboratory of Precision Medicine for Atherosclerotic Diseases of Zhejiang Province, Ningbo, Zhejiang Province, China
  • Online:2026-04-15 Published:2025-07-26
  • Contact: Xiang Gao, MD, fyygaoxiang@nbu.edu.cn; Yi Huang, PhD, huangy102@gmail.com.
  • Supported by:
    This work was supported by grants from the Zhejiang Provincial TCM Science and Technology Plan Project, No. 2023ZL156 (to YH); Ningbo Top Medical and Health Research Program, No. 2022020304 (to XG); and the Natural Science Foundation of Ningbo, No. 2023J019 (to YH); Key Laboratory of Precision Medicine for Atherosclerotic Diseases of Zhejiang Province, No. 2022E10026 (to YH).

摘要:

脑卒中包括缺血性脑卒中(IS)和出血性脑卒中病理生理机制错综复杂,包括氧化应激、炎症、线粒体功能障碍和神经元损伤。核因子红细胞 2 相关因子 2(NRF2)和核因子-kappaB(NF-κB)等关键转录因子在脑卒中的进展过程中起着核心作用。具体来说,NRF2 是一种对细胞氧化还原状态变化敏感的转录因子,在保护细胞免受氧化损伤、炎症反应和有害细胞毒素的作用中至关重要。它通过影响线粒体功能、内质网应激、溶酶体活性以及调节代谢途径和细胞因子的表达,在脑卒中后的神经保护和修复中发挥着重要作用。相反,NF-κB 作为一种关键的炎症调节转录因子,与线粒体功能障碍、活性氧的产生密切相关,并加剧了脑组织中的氧化应激和炎症。NF-κB 还通过调节细胞粘附分子和炎症介质,导致脑卒中后神经元损伤、凋亡和免疫反应。这些通路之间的相互作用,可能涉及各种细胞器之间的交叉对话,对脑卒中的病理生理学产生重大影响。此外,单细胞测序和空间转录组学的进步大大提高了我们对脑卒中发病机制的认识,为开发有针对性的、个体化的、细胞类型特异性治疗提供了新的机遇。这篇综述讨论了 NRF2 和 NF-κB 在缺血性和出血性脑卒中中的作用机制,重点是它们在氧化应激、炎症和神经保护中的作用。

https://orcid.org/0000-0002-6844-9651 (Xiang Gao); https://orcid.org/0000-0003-3598-9747 (Yi Huang)

关键词: 脑卒中, 氧化应激, 炎症, 核因子红细胞2相关因子2(NRF2), 核因子κB, 细胞器

Abstract: Strokes include both ischemic stroke, which is mediated by a blockade or reduction in the blood supply to the brain, and hemorrhagic stroke, which comprises intracerebral hemorrhage and subarachnoid hemorrhage and is characterized by bleeding within the brain. Stroke is a lifethreatening cerebrovascular condition characterized by intricate pathophysiological mechanisms, including oxidative stress, inflammation, mitochondrial dysfunction, and neuronal injury. Critical transcription factors, such as nuclear factor erythroid 2-related factor 2 and nuclear factor kappa B, play central roles in the progression of stroke. Nuclear factor erythroid 2-related factor 2 is sensitive to changes in the cellular redox status and is crucial in protecting cells against oxidative damage, inflammatory responses, and cytotoxic agents. It plays a significant role in post-stroke neuroprotection and repair by influencing mitochondrial function, endoplasmic reticulum stress, and lysosomal activity and regulating metabolic pathways and cytokine expression. Conversely, nuclear factor-kappaB is closely associated with mitochondrial dysfunction, the generation of reactive oxygen species, oxidative stress exacerbation, and inflammation. Nuclear factor-kappaB contributes to neuronal injury, apoptosis, and immune responses following stroke by modulating cell adhesion molecules and inflammatory mediators. The interplay between these pathways, potentially involving crosstalk among various organelles, significantly influences stroke pathophysiology. Advancements in single-cell sequencing and spatial transcriptomics have greatly improved our understanding of stroke pathogenesis and offer new opportunities for the development of targeted, individualized, cell typespecific treatments. In this review, we discuss the mechanisms underlying the involvement of nuclear factor erythroid 2-related factor 2 and nuclear factor-kappa B in both ischemic and hemorrhagic stroke, with an emphasis on their roles in oxidative stress, inflammation, and neuroprotection.

Key words: inflammation, nuclear factor erythroid 2-related factor 2, nuclear factor-kappa B, organelles, oxidative stress, stroke