Spinal cord injury (SCI) is a devastating event which caused high mortality and morbidity. Recently, nucleotide-binding domain-like receptor protein 3 (NLRP3) inflammasome has been showed to act a critical t role in the secondly injury phase of SCI. In current study, we aimed to investigate the effect and underlying molecular mechanisms of extracellular vesicles derived from epidural fat (EF)- mesenchymal stem cells (MSCs) for the treatment of SCI. Ninety-six Sprague-Dawley rats were used for current study and randomly divided into four groups: sham group, SCI group, SCI + Saline group, SCI + Extracellular vesicles group. Basso-Beattie-Bresnahan (BBB) scores was applied to evaluate the neurological functional recovery. Cresyl violet-stained was conducted evaluate the protective effect of EF-MSCs-Extracellular vesicles on lesion volume after SCI. ELISA, immunohistochemistry assay, TUNEL assay and western blotting were conducted to investigate the underlying molecular mechanisms. Our results demonstrated that the administration of EF-MSCs-Extracellular vesicles via tail vein injection improved neurological functional recovery and reduced the lesion volume after SCI. And systemic administration of EF-MSCs-Extracellular vesicles significantly inhibited NLRP3 inflammasome activation and reduced the expression of inflammatory cytokines. Additionally, the expression levels of proapoptotic protein Bax was decreased and antiapoptotic Bcl-2 was upregulated with the treatment of EF-MSCs-Extracellular vesicles after SCI. In summary, in current study, we demonstrated for the first time that the EF-MSCs-Extracellular vesicles can improve neurological functional recovery after SCI, and the underlying molecular mechanisms may partly through the inhibition of NLRP3 inflammasome activation.

中文翻译：

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硬膜外脂肪间充质干细胞衍生的细胞外囊泡可减轻NLRP3炎性小体的活化并改善脊髓损伤后的功能恢复。

脊髓损伤（SCI）是一个破坏性事件，导致高死亡率和高发病率。最近，已显示核苷酸结合结构域样受体蛋白3（NLRP3）炎性小体在SCI的第二损伤阶段起着关键性的作用。在当前的研究中，我们旨在研究源自硬膜外脂肪（EF）-间充质干细胞（MSCs）的细胞外囊泡治疗SCI的作用及其潜在的分子机制。将96只Sprague-Dawley大鼠用于本研究，并随机分为四组：假手术组，SCI组，SCI +盐水组，SCI +细胞外囊泡组。Basso-Beattie-Bresnahan（BBB）评分用于评估神经功能恢复。进行甲酚紫染色以评估EF-MSCs-细胞外囊泡对SCI后病变体积的保护作用。进行了ELISA，免疫组织化学测定，TUNEL测定和蛋白质印迹以研究潜在的分子机制。我们的结果表明，通过尾静脉注射施用EF-MSCs-细胞外囊泡可改善神经功能恢复并减少SCI后的病变体积。EF-MSCs-细胞外囊泡的全身性给药可显着抑制NLRP3炎性小体的活化并降低炎性细胞因子的表达。此外，SCI后EF-MSCs-细胞外囊泡的处理可降低促凋亡蛋白Bax的表达水平，并上调抗凋亡Bcl-2。总而言之，在当前的研究中，我们首次证明EF-MSCs-细胞外囊泡可以改善SCI后的神经功能恢复，