中国神经再生研究(英文版)

中国神经再生研究(英文版) ›› 2025, Vol. 20 ›› Issue (4): 1178-1191.doi: 10.4103/NRR.NRR-D-23-01299

• 原著:退行性病与再生 • 上一篇    下一篇

全氟戊烷载氧纳米液滴抑制小胶质细胞活化的新机制

  

  • 出版日期:2025-04-15 发布日期:2024-07-03

Perfluoropentane-based oxygen-loaded nanodroplets reduce microglial activation through metabolic reprogramming

Wanxian Luo1, #, Chuanhui Xu2, #, Linxi Li2, Yunxiang Ji2, Yezhong Wang2, Yingjia Li1, *, Yongyi Ye2, *   

  1. 1Department of Medicine Ultrasonics, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong Province, China; 2Institute of Neuroscience, Department of Neurosurgery, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong Province, China
  • Online:2025-04-15 Published:2024-07-03
  • Contact: Yongyi Ye, MD, PhD, yeyongyi@gzhmu.edu.cn; Yingjia Li, MD, PhD, lyjia@smu.edu.cn.
  • Supported by:
    This study was supported by the National Natural Science Foundation of China, No. 82101327 (to YY); President Foundation of Nanfang Hospital, Southern Medical University, No. 2020A001 (to WL); Guangdong Basic and Applied Basic Research Foundation, Nos. 2019A1515110150, 2022A1515012362 (both to YY); and Guangzhou Science and Technology Project, No. 202201020111 (to YY).

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摘要：

小胶质细胞是大脑中主要的常驻免疫细胞，常被认为是治疗中枢神经系统内神经退行性疾病（包括帕金森病）的一个潜在的靶点。纳米级别的全氟碳液滴不仅具有高效载氧能力，并且一些全氟碳液滴还展现出强大抗炎效应。然而，全氟戊烷在小胶质细胞介导的中枢炎症反应中的作用仍缺乏相关研究。此次实验构建了一种纳米级全氟碳液滴—全氟戊烷载氧纳米液滴。实验发现这种全氟戊烷载氧纳米液滴预处理可有效抑制小胶质细胞M1型活化，抑制其炎症反应、氧化应激和细胞迁移能力，降低其神经毒性效应，继而发挥神经保护效应。此外，基于超高效液相-串联质谱的代谢组学研究发现，全氟戊烷载氧纳米液滴的抗炎作用主要是由小胶质细胞代谢重编程的调节引起的。且进一步证实AKT-mTOR-缺氧诱导因子1α信号通路可介导此代谢重编程过程。因此，实验构建的新型全氟戊烷载氧纳米液滴可通过代谢重编程缓解小胶质细胞介导的中枢炎症反应。

https://orcid.org/0009-0004-9140-463X (Yongyi Ye); https://orcid.org/0000-0002-8885-2317 (Yingjia Li)

关键词: 帕金森病, 小胶质细胞, 神经炎症, 小胶质迁移, 全氟戊烷, 载氧纳米液滴, 代谢重编程, 超高效液相-串联质谱, 纳米疗法, 神经退行性疾病

Abstract: Microglia, the primary immune cells within the brain, have gained recognition as a promising therapeutic target for managing neurodegenerative diseases within the central nervous system, including Parkinson’s disease. Nanoscale perfluorocarbon droplets have been reported to not only possess a high oxygen-carrying capacity, but also exhibit remarkable anti-inflammatory properties. However, the role of perfluoropentane in microglia-mediated central inflammatory reactions remains poorly understood. In this study, we developed perfluoropentane-based oxygen-loaded nanodroplets (PFP-OLNDs) and found that pretreatment with these droplets suppressed the lipopolysaccharide-induced activation of M1-type microglia in vitro and in vivo, and suppressed microglial activation in a mouse model of Parkinson’s disease. Microglial suppression led to a reduction in the inflammatory response, oxidative stress, and cell migration capacity in vitro. Consequently, the neurotoxic effects were mitigated, which alleviated neuronal degeneration. Additionally, ultrahigh-performance liquid chromatography–tandem mass spectrometry showed that the anti-inflammatory effects of PFP-OLNDs mainly resulted from the modulation of microglial metabolic reprogramming. We further showed that PFP-OLNDs regulated microglial metabolic reprogramming through the AKT-mTOR-HIF-1α pathway. Collectively, our findings suggest that the novel PFP-OLNDs constructed in this study alleviate microglia-mediated central inflammatory reactions through metabolic reprogramming.

Key words: metabolic reprogramming, microglia, microglial migration, nanotherapy, neurodegenerative diseases, neuroinflammation, oxygen-loaded nanodroplets, Parkinson’s disease, perfluoropentane, ultra-performance liquid chromatography–mass spectrometry