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基于全氟戊烷的载氧纳米液滴通过代谢重编程减少小胶质细胞活化。

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

作者信息

Luo Wanxian, Xu Chuanhui, Li Linxi, Ji Yunxiang, Wang Yezhong, Li Yingjia, Ye Yongyi

机构信息

Department of Medicine Ultrasonics, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong Province, China.

Institute of Neuroscience, Department of Neurosurgery, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong Province, China.

出版信息

Neural Regen Res. 2025 Apr 1;20(4):1178-1191. doi: 10.4103/NRR.NRR-D-23-01299. Epub 2024 Apr 3.

DOI:10.4103/NRR.NRR-D-23-01299
PMID:38989955
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11438333/
Abstract

JOURNAL/nrgr/04.03/01300535-202504000-00032/figure1/v/2024-07-06T104127Z/r/image-tiff 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.

摘要

小胶质细胞是大脑中的主要免疫细胞，已成为治疗包括帕金森病在内的中枢神经系统神经退行性疾病的一个有前景的治疗靶点。据报道，纳米级全氟碳液滴不仅具有高携氧能力，还具有显著的抗炎特性。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知之甚少。在本研究中，我们开发了基于全氟戊烷的载氧纳米液滴（PFP-OLNDs），并发现用这些液滴预处理可在体外和体内抑制脂多糖诱导的M1型小胶质细胞活化，并在帕金森病小鼠模型中抑制小胶质细胞活化。小胶质细胞的抑制导致体外炎症反应、氧化应激和细胞迁移能力降低。因此，神经毒性作用得到减轻，从而减轻了神经元变性。此外，超高效液相色谱-串联质谱显示，PFP-OLNDs的抗炎作用主要源于对小胶质细胞代谢重编程的调节。我们进一步表明，PFP-OLNDs通过AKT-mTOR-HIF-1α途径调节小胶质细胞代谢重编程。总的来说，我们的研究结果表明，本研究构建的新型PFP-OLNDs通过代谢重编程减轻小胶质细胞介导的中枢炎症反应。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0f28/11438333/b0559aa7623a/NRR-20-1178-g010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0f28/11438333/5de5b1154a0e/NRR-20-1178-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0f28/11438333/de09e2d754f1/NRR-20-1178-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0f28/11438333/e7c2bb80b446/NRR-20-1178-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0f28/11438333/942e35547bfc/NRR-20-1178-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0f28/11438333/de831a375f77/NRR-20-1178-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0f28/11438333/acaba3457893/NRR-20-1178-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0f28/11438333/037d94df92bb/NRR-20-1178-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0f28/11438333/b254db68f6f7/NRR-20-1178-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0f28/11438333/b0559aa7623a/NRR-20-1178-g010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0f28/11438333/5de5b1154a0e/NRR-20-1178-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0f28/11438333/de09e2d754f1/NRR-20-1178-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0f28/11438333/e7c2bb80b446/NRR-20-1178-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0f28/11438333/942e35547bfc/NRR-20-1178-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0f28/11438333/de831a375f77/NRR-20-1178-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0f28/11438333/acaba3457893/NRR-20-1178-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0f28/11438333/037d94df92bb/NRR-20-1178-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0f28/11438333/b254db68f6f7/NRR-20-1178-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0f28/11438333/b0559aa7623a/NRR-20-1178-g010.jpg

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