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 (6): 2370-2379.doi: 10.4103/NRR.NRR-D-24-01260

• 原著:脑损伤修复保护与再生 • 上一篇    下一篇

间充质干细胞来源细胞外囊泡中的miRNA在雌性小鼠慢性饮酒诱导的神经炎症和行为障碍中的作用

  

  • 出版日期:2026-06-15 发布日期:2026-04-17

Role of miRNAs from mesenchymal stem cell-derived extracellular vesicles in neuroinflammation and behavioral impairments induced by chronic alcohol consumption in female mice

Susana Mellado1, Najoua Touahri1, Sandra Montagud-Romero2, Carla Perpiñá-Clérigues1, 3, Francisco García-García3, Victoria Moreno-Manzano4, Consuelo Guerri1, Marta Rodríguez-Arias2, María Pascual1, *   

  1. 1Department of Physiology, School of Medicine and Dentistry, University of Valencia, Valencia, Spain;  2Department of Psychobiology, School of Psychology, University of Valencia, Valencia, Spain;  3Computational Biomedicine Laboratory, Príncipe Felipe Research Center, Valencia, Spain;  4Neuronal and Tissue Regeneration Laboratory, Príncipe Felipe Research Center, Valencia, Spain
  • Online:2026-06-15 Published:2026-04-17
  • Contact: María Pascual, PhD, maria.pascual@uv.es.
  • Supported by:
    This work was supported by the Spanish Ministry of Health‐Plan Nacional sobre Drogas (2023‐I024), the the Ministry of Science, Innovation and Universities/State Research Agency/10.13039/501100011033 (PID2023-146865OB-I00), Generalitat Valenciana (CIAICO/2021/203), the Primary Addiction Care Research Network (RD21/0009/0005) and FEDER Funds, GVA. 

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摘要：

间充质干细胞来源的细胞外囊泡已成为一种极具前景的再生和免疫调节疗法；事实上，间充质干细胞来源的细胞外囊泡中所含的微RNA（miRNA）能够调节靶基因的表达，并影响与疾病相关的信号通路。慢性饮酒会导致神经炎症、脑损伤及认知功能障碍。现有证据表明，雌性动物比雄性动物更易受到酒精诱导的损伤。尽管间充质干细胞来源的外泌体已在多种神经炎症病症中得到研究，但其对抗酒精诱导的脑损伤的潜力尚不明确。本研究旨在探究反复静脉注射间充质干细胞来源的外泌体能否改善雌性小鼠因长期饮酒引发的神经炎症及行为障碍。通过分析乙醇处理小鼠的全脑3D图像及脑冠状切片，发现间充质干细胞来源的外泌体显著降低了微型正电子发射断层扫描示踪剂（18F-FDG）的结合水平。间充质干细胞来源的外泌体给药可抵御乙醇诱导的促炎基因上调、认知功能障碍以及可卡因的条件性奖赏效应。间充质干细胞来源外泌体的miRNA测序数据表明，在接受间充质干细胞来源外泌体给药后，乙醇处理雌性小鼠脑内外泌体来源的miR-483-5p和miR-140-3p表达水平升高。此外，间充质干细胞来源的外泌体还调节了乙醇处理雌性小鼠脑内与促炎相关的miRNA靶基因（如Socs3、Tnf、Mtor和Atf6）的表达。这些结果表明，间充质干细胞来源的细胞外囊泡可作为一种神经保护疗法，以缓解慢性酒精摄入引发的神经炎症、认知功能障碍以及可卡因的条件性奖励效应。

https://orcid.org/0000-0003-1420-631X (María Pascual)


关键词: 行为, 慢性酒精摄入, 认知, 乙醇, 细胞外囊泡, 雌性, 间充质干细胞, miRNA, 神经炎症

Abstract: Mesenchymal stem cell-derived extracellular vesicles have emerged as a promising form of regenerative and immunomodulatory therapy; indeed, micro (mi)RNAs contained within mesenchymal stem cell-derived extracellular vesicles modulate target gene expression and impact disease-associated pathways. Chronic alcohol consumption leads to neuroinflammation, brain damage, and impaired cognition. Evidence indicates that females are more vulnerable to alcohol-induced damage than males. While mesenchymal stem cell-derived extracellular vesicles have been studied in various neuroinflammatory conditions, their potential to counteract alcohol-induced brain damage remains unclear. In this study, we investigated whether repeated intravenous administration of mesenchymal stem cell-derived extracellular vesicles could ameliorate neuroinflammation and behavioral impairment induced by chronic alcohol consumption in female mice. Mesenchymal stem cell-derived extracellular vesicles diminished the increased binding of a micro-positron emission tomography tracer (18F-FDG) when analyzing whole-brain 3D images and brain coronal sections of ethanol-treated mice. Mesenchymal stem cell-derived extracellular vesicle administration protected against ethanol-induced proinflammatory gene upregulation, cognitive dysfunction, and the conditioned rewarding effects of cocaine. MiRNA sequencing data from mesenchymal stem cell-derived extracellular vesicles revealed the elevated expression of extracellular vesicle-derived miR-483-5p and miR-140-3p in the brains of ethanol-treated female mice following mesenchymal stem cell-derived extracellular vesicle administration. In addition, mesenchymal stem cell-derived extracellular vesicles modulated the expression of pro-inflammatory-related miRNA target genes (e.g., Socs3, Tnf, Mtor, and Atf6) in the brains of ethanol-treated female mice. These results suggest that mesenchymal stem cell-derived extracellular vesicles could function as a neuroprotective therapy to ameliorate the neuroinflammation, cognitive dysfunction, and conditioned rewarding effects of cocaine associated with chronic alcohol consumption.

Key words: behavior, chronic alcohol consumption, cognitive, ethanol, extracellular vesicles, female, mesenchymal stem cells, miRNAs, neuroinflammation