中国神经再生研究(英文版) ›› 2026, Vol. 21 ›› Issue (7): 3225-3237.doi: 10.4103/NRR.NRR-D-24-01532

• 原著:脑损伤修复保护与再生 • 上一篇    下一篇

热休克蛋白β1抑制小胶质细胞铁死亡和促炎性活化可减轻脑缺血再灌注损伤#br#
#br#

  

  • 出版日期:2026-07-15 发布日期:2026-03-31
  • 基金资助:
    上海市“曙光计划”(22SG37)和国家自然科学基金项目(8237131382401536

Hspb1 inhibits microglial ferroptosis and pro-inflammatory activation to alleviate cerebral ischemia/reperfusion injury in mice

Weilong Hua1, #, Hongye Xu1, 2, #, Rundong Chen1, 3, #, Yiyong Zeng1, 4, Lei Zhang1, Yongxin Zhang1, Xiaoxi Zhang1, Yongwei Zhang1, Hongjian Zhang1, 5, 6, *, Jianmin Liu1, 5, Pengfei Yang1, 5, *#br#

#br#
  

  1. 1Neurovascular Center, Changhai Hospital, Naval Medical University, Shanghai, China; 
    2Department of Neurology, No. 904 Hospital of the PLA Joint Logistics Support Force, Wuxi, Jiangsu Province, China; 
    3School of Health Science and Engineering, University of Shanghai for Science and Technology, Shanghai, China; 
    4Department of Neurosurgery, the First Affiliated Hospital of Ningbo University, Ningbo, Zhejiang Province, China; 
    5Oriental Pan-Vascular Devices Innovation College, University of Shanghai for Science and Technology, Shanghai, China; 6Department of Neurosurgery, Shidong Hospital Affiliated to University of Shanghai for Science and Technology, Shanghai, China

  • Online:2026-07-15 Published:2026-03-31
  • Contact: Hongjian Zhang, MD, chzhanghj2012@me.com; Pengfei Yang, MD, chyangpf@163.com.
  • Supported by:
    This study was supported by the “Dawn” Program of Shanghai Education Commission, No. 22SG37 (to PY); the National Natural Science Foundation of China, Nos. 82371313 (to PY), 82401536 (to YongxinZ).

摘要:

热休克蛋白β1可能参与调控细胞的铁死亡过程。有研究表明Hspb1表达在脑卒中后上调。但是,热休克蛋白β1在脑缺血再灌注损伤中的具体作用机制尚不清楚,需要进一步研究以阐明。实验通过使用脑缺血损伤的体内和体外模型:C57BL/6J小鼠的大脑中动脉阻塞再灌注和BV-2小胶质细胞的氧糖剥夺复氧复糖。结果发现,热休克蛋白β1的过表达显著缩小了模型小鼠的脑梗死体积,减轻了神经元丢失,并改善了神经功能预后。机制上,热休克蛋白β1通过抑制小胶质细胞中的脂质过氧化、细胞内铁积累及活性氧生成,同时增强GPX4表达并抑制核因子κB通路激活,发挥保护作用。值得注意的是,使用佛波酯12-肉豆蔻酸酯13-乙酸酯(phorbol 12-myristate 13-acetate)药理学激活核因子κB可逆转热休克蛋白β1的保护效应,证实该通路的功能相关性。总之,热休克蛋白β1通过调节核因子κB/GPX4信号轴,抑制小胶质细胞的铁死亡和促炎性活化,从而对脑缺血再灌注损伤发挥神经保护作用。这些发现确立了热休克蛋白β1作为小胶质细胞中核因子κB/GPX4轴的关键调节因子,为抑制缺血性脑卒中的铁死亡和炎症提供了双靶点策略。


https://orcid.org/0000-0002-1937-2766 (Hongjian Zhang); 

https://orcid.org/0000-0002-6154-3602 (Pengfei Yang)

关键词: 脑缺血再灌注, Hspb1, 炎症, 小胶质细胞铁死亡, NF-κB/GPX4信号轴

Abstract:

Investigating the mechanisms underlying central nervous system disorders is a major scientific issue in the 21st century. However, the inaccessibility and complexity of the human brain have always represented a challenge in understanding the pathophysiology of the central nervous system. Brain organoids are self-assembled three-dimensional aggregates derived from pluripotent stem cells with cell types and structures similar to the embryonic human brain, giving them potential for investigating the atypical cellular, molecular, and genetic characteristics characteristic of central nervous system disorders. Brain organoids also provide a platform for drug screening and serve as a potential source for transplantation therapy for brain injuries. However, the broad application of brain organoids is hampered by several limitations, such as the lack of high-fidelity cell types, insufficient maturation, and considerable heterogeneity, undermining their reliability in specific applications. This review summarizes brain organoid evolution, discusses recent technological and methodological innovations, and reviews their applications in drug screening, transplantation therapy, and disease modeling, as well as clinical research progress. Additionally, we emphasize the limitations of current brain organoid research and explore the potential for advancing the technology to enhance its applicability.

Key words: acute brain injury, bioengineering, brain organoids, brain tissue transplantation, cerebral organoids, drug screening, induced pluripotent stem cell, neurodegenerative diseases, neurodevelopmental disorders