医学研究与教育 ›› 2022, Vol. 39 ›› Issue (2): 1-9.DOI: 10.3969/j.issn.1674-490X.2022.02.001

• 基础医学 •    下一篇

Nrf2在缺血性脑损伤中的关键性作用

朱健平,李运曼   

  1. 中国药科大学基础医学与临床药学学院, 江苏 南京 210009
  • 收稿日期:2022-01-21 出版日期:2022-04-25 发布日期:2022-04-25
  • 通讯作者: 李运曼(1957—),女,河北石家庄人,教授,博士生导师,主要从事心脑血管疾病及肿瘤多药耐药逆转剂的药理研究。E-mail: liyunman@cpu.edu.cn
  • 作者简介:朱健平(1997—),男,江苏淮安人,在读硕士。
  • 基金资助:
    国家科学技术部十三五“重大新药创制”重大专项项目基金(2019ZX09301-134)

The key role of Nrf2 in ischemic stroke

ZHU Jianping, LI Yunman   

  1. School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing 210009, China
  • Received:2022-01-21 Online:2022-04-25 Published:2022-04-25

摘要: 缺血性脑卒中是全球范围内致死及致残的主要原因之一。核因子E2相关因子2(nuclear factor-erythroid 2-related factor 2,Nrf2)是一种调节机体氧化还原反应平衡的蛋白质分子,通过协调多种细胞保护基因,参与抵抗内源性或外源性压力。Nrf2 信号通路不仅严格调控机体氧化还原稳态,同时还参与调节机体代谢的多个过程。因此,靶向 Nrf2 已成为预防和治疗包括缺血性脑卒中在内的中枢神经系统疾病的潜在策略。首先介绍 Nrf2 和 Kelch 样 ECH 相关蛋白 1(Kelch-like ECH-associated protein 1,Keap1)的结构特征,并简要描述 Nrf2 通路的激活和调控过程。然后讨论 Nrf2 通路的病理生理机制、上游调节剂和下游靶点。在此背景下,扩展到 Nrf2 在缺血性脑卒中后的作用,并探讨潜在的治疗方向。

关键词: 缺血性脑卒中, 核因子E2相关因子2, 氧化应激, 神经炎症, 血-脑脊液屏障

Abstract: Ischemic stroke is one of the main causes of death and disability worldwide. Nuclear factor E2-related factor 2(Nrf2)is an important transcription factor that regulates the balance of the body's redox reaction. It participates in resisting endogenous or exogenous stress by coordinating a variety of cytoprotective genes. The Nrf2 signaling pathway not only strictly regulates the body's redox homeostasis, but also participates in the regulation of multiple processes in the body metabolism. Therefore, targeting Nrf2 has become a potential strategy for the prevention and treatment of central nervous system diseases including ischemic stroke. In this review, we first introduced the structural features of Nrf2 and Kelch-like ECH-related protein 1(Keap1), and briefly described the activation and regulation of the Nrf2 pathway. Next, we discussed the pathological and physiological mechanism, upstream regulators and downstream targets of the Nrf2 pathway. In this context, we extended the discussion to the role of Nrf2 after ischemic stroke and explored potential therapeutic directions.

Key words: ischemic stroke, Nrf2, oxidative stress, neuroinflammation, blood-brain barrier

中图分类号: