Abstract：
Cerebral ischemia-reperfusion injury (I/RI) is one of the principal pathogenic factors in the poor prognosis of ischemic stroke, for which current therapeutic options to enhance neurological recovery are notably insufficient. Dental pulp stem cell-derived extracellular vesicles (DPSC-EVs) have promising prospects in stroke treatment and the specific underlying mechanisms have yet to be fully elucidated. The present study observed that DPSC-EVs ameliorated the degree of cerebral edema and infarct volume by reducing the apoptosis of neurons. Furthermore, the miRNA sequencing and functional enrichment analysis identified that miR-877-3p as a key component in DPSC-EVs, contributing to neuroprotection and anti-apoptotic effects. Following target prediction and dual-luciferase assay indicated that miR-877-3p interacted with Bcl-2-associated transcription factor (Bclaf1) to play a function. The miR-877-3p inhibitor or Bclaf1 overexpression reversed the neuroprotective effects of DPSC-EVs. The findings reveal a novel therapeutic pathway where miR-877-3p, transferred via DPSC-EVs, confers neuroprotection against cerebral I/RI, highlighting its potential in promoting neuronal survival and recovery post-ischemia.
摘要：
脑缺血再灌注损伤(I/RI)是缺血性脑卒中预后不良的主要致病因素之一。目前用于增强神经系统恢复的治疗方案明显不足。牙髓干细胞衍生的细胞外囊泡（DPSC-EV）在中风治疗中具有广阔的前景，其具体的潜在机制尚未完全阐明。本研究观察到DPSC-EV通过减少神经元的凋亡来改善脑水肿和梗死体积的程度。此外，miRNA测序和功能富集分析确定miR-877-3p是DPSC-EV的关键成分，有助于神经保护和抗凋亡作用。靶标预测和双荧光素酶实验表明miR-877-3p与Bcl-2相关转录因子（Bclaf1）相互作用发挥功能。miR-877-3p抑制剂或Bclaf1过表达逆转了DPSC-EV的神经保护作用。研究结果揭示了一种新的治疗途径，其中miR-877-3p，通过DPSC-EV传输，赋予对脑I/RI的神经保护，强调其在促进神经元存活和缺血后恢复方面的潜力。
