Department of Orthopaedics, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China.
Department of Orthopaedics, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China.
Free Radic Biol Med. 2023 Nov 1;208:319-333. doi: 10.1016/j.freeradbiomed.2023.08.026. Epub 2023 Aug 26.
Although spinal cord injury (SCI) represents a primary etiology of disability, currently, there are exist limited viable therapies modalities. Acquiring comprehension of the diverse pathways that drive mitochondrial aberration may facilitate the identification of noteworthy targets for ameliorating the deleterious consequences precipitated by SCI. Our objective was to determine the efficiency of exosomes produced from Schwann cells (SCDEs) in protecting against mitochondrial dysfunction. This evaluation was conducted using a rat model of compressed SCI and in vitro experiments involving rat pheochromocytoma cells (PC12) exposed to oxygen-glucose deprivation (OGD). The conducted experiments yielded evidence that SCDEs effectively mitigated oxidative stress (OS) and inflammation subsequent to SCI, while concurrently diminishing necroptosis. Subsequent in vitro inquiry assessed the impact of SCDEs on PC12, with a specific emphasis on mitochondrial functionality, necrotic cell prevalence, and mitophagy. The study findings revealed that SCDEs enhanced mitophagy in PC12 cells, leading to a decrease in the generation of reactive oxygen species (ROS) and inflammatory cytokines (CK) provoked by OGD-induced injury. This, in turn, mitigated mitochondrial dysfunction and necroptosis. Mechanistically, SCDEs facilitated cellular mitophagy through activation of the AMPK signaling pathway. In conclusion, our data strongly support the notion that SCDEs hold considerable promise as a therapeutic approach for managing SCI. Furthermore, our investigation serves to elucidate the pivotal role of AMPK-mediated mitophagy in reducing cell damage, thereby unveiling novel prospects for enhancing neuro-pathological outcomes following SCI.
虽然脊髓损伤（SCI）是导致残疾的主要病因，但目前可用的治疗方法非常有限。深入了解导致线粒体异常的不同途径，可能有助于确定改善 SCI 引发的有害后果的有意义靶点。我们的目标是确定施万细胞（SCDE）来源的外泌体在预防线粒体功能障碍中的效率。为此，我们采用大鼠压缩性 SCI 模型和体外实验，研究了大鼠嗜铬细胞瘤细胞（PC12）在氧葡萄糖剥夺（OGD）条件下的反应。实验结果表明，SCDE 可有效减轻 SCI 后的氧化应激（OS）和炎症，同时减少坏死性凋亡。随后的体外研究评估了 SCDE 对 PC12 的影响，特别关注线粒体功能、坏死细胞比例和自噬。研究发现，SCDE 增强了 PC12 细胞的自噬作用，减少了 OGD 诱导损伤引起的活性氧（ROS）和炎症细胞因子（CK）的产生。这反过来又减轻了线粒体功能障碍和坏死性凋亡。从机制上讲，SCDE 通过激活 AMPK 信号通路促进细胞自噬。总之，我们的数据强烈支持 SCDE 作为治疗 SCI 的一种有前途的方法的观点。此外，我们的研究阐明了 AMPK 介导的自噬在减轻细胞损伤中的关键作用，为改善 SCI 后的神经病理结果提供了新的前景。
