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 (8): 3569-3578.doi: 10.4103/NRR.NRR-D-24-00837

• 原著:脑损伤修复保护与再生 • 上一篇    下一篇

锰铁普鲁士蓝纳米酶减轻缺血性脑卒中损伤的作用机制

  

  • 出版日期:2026-08-18 发布日期:2026-04-27

Elucidation of the mechanism by which manganese-iron Prussian blue nanozymes alleviate ischemic stroke damage in a mouse model

Xue Li1, 2, 3, #, Chengyun Hu1, 2, 3, #, Shanshan Luo1, 2, #, Yanhong Zhang1, 2, Bilu Li1, 2, Chao Wu1, 2, Zhengyan Wu3, Jia Zhang3, *, Chaoliang Tang1, 2, *   

  1. 1Department of Anesthesiology, The First Affiliated Hospital of University of Science and Technology of China, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui Province, China;
     2Department of Anesthesiology, Anhui Provincial Cancer Hospital, Hefei, Anhui Province, China; 
    3Institute of Intelligent Machines, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei, Anhui Province, China
  • Online:2026-08-18 Published:2026-04-27
  • Contact: Chaoliang Tang, MD, PhD, chaolt@ustc.edu.cn; Jia Zhang, PhD, zhangj@iim.ac.cn.
  • Supported by:
    This study was supported by the Natural Science Foundation of Anhui Province of China, No. 2208085Y32; Scientific Research Plan Project of Anhui Province of China, No. 2022AH020076; and the Chen Xiao-Ping Foundation for the Development of Science and Technology of Hubei Province, No. CXPJJH12000005-07-115 (all to CT).
     

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摘要：

缺血性脑卒中后神经免疫炎症反应以及肠道微生物群失调，被认为是其进展和不良预后的重要原因。作者既往研究构建了一种锰铁普鲁士蓝纳米酶，其为一类具有多酶结构和多孔结构的新型纳米酶，具有显著的抗氧化能力。但是锰铁普鲁士蓝纳米酶是否对缺血性脑卒中有治疗作用及其机制尚不明确。为此，实验构建了大脑中动脉阻塞小鼠模型，灌胃锰铁普鲁士蓝纳米酶进行治疗。结果发现，锰铁普鲁士蓝纳米酶可显著减轻大脑中动脉阻塞小鼠的梗死体积，改善神经功能，并恢复肠道微生物群平衡，提高短链脂肪酸水平。进一步在脂多糖诱导BV-2细胞体外模型中发现，锰铁普鲁士蓝纳米酶可显著抑制Toll样受体4/核因子κB信号通路中TLR4、IKKα和pp65水平。由此提示，锰铁普鲁士蓝纳米酶通过调节Toll样受体4/核因子κB信号通路来纠正肠道菌群紊乱，增加短链脂肪酸含量，从而治疗缺血性脑卒中。


https://orcid.org/0000-0002-4697-8237 (Jia Zhang); https://orcid.org/0000-0002-1936-028X (Chaoliang Tang)

关键词: 锰铁普鲁士蓝纳米酶, 缺血性脑卒中, 神经功能, 肠道微生物群, 短链脂肪酸, 炎症反应, 氧化应激, Toll样受体4, 核因子κB, BV-2细胞

Abstract: Ischemic stroke represents a significant global health challenge, frequently associated with intricate pathophysiological alterations. During ischemic stroke, the generation of reactive oxygen species markedly increases, leading to direct neuronal damage as well as initiating a cascade of inflammatory responses. This oxidative stress can also disturb the equilibrium of the gut microbiota, resulting in dysbiosis. In turn, an imbalance in gut microbiota can further exacerbate the production of reactive oxygen species and contribute to a pro-inflammatory environment within the body. This creates a vicious cycle that not only promotes the progression of stroke but also leads to adverse functional outcomes. The neuroinflammation and intestinal microbiota dysbiosis that occur following ischemic stroke are critical contributors to stroke progression and adverse functional outcomes. We previously developed manganese-ferric Prussian blue nanozymes, characterized by a multi-enzyme structure and a porous design, that exhibit strong antioxidant properties. However, the therapeutic effects of manganese-ferric Prussian blue nanozymes on ischemic stroke and their mechanisms of action remain have not been fully elucidated. To investigate this, we constructed a mouse model of middle cerebral artery occlusion and administered manganese-ferric Prussian blue nanozymes via gastric gavage. Our results demonstrated that these nanozymes substantially reduced infarct volume, improved neurological function, restored gut microbiota balance, and increased levels of short-chain fatty acids in the mouse model. Treatment of lipopolysaccharide-treated BV-2 cells with short-chain fatty acids markedly decreased the expression levels of components of the Toll-like receptor 4/nuclear factor kappa B signaling pathway, including Toll-like receptor 4, inhibitor of nuclear factor kappa-B kinase subunit alpha, and pp65. These findings suggest that manganese-ferric Prussian blue nanozymes can correct gut microbiota dysbiosis and increase short-chain fatty acid production by modulating the Toll-like receptor 4/nuclear factor kappa B signaling pathway, thereby providing therapeutic benefits in the context of ischemic stroke. 

Key words: BV-2 cells, gut microbiota, inflammatory response, ischemic stroke, manganese-iron Prussian blue nanozymes, neurological function, nuclear factor-κB, oxidative stress, short-chain fatty acids, Toll-like receptor 4