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骨髓间充质干细胞来源的外泌体通过 miR-497-5p/TXNIP/NLRP3 轴促进脊髓损伤修复。

Bone marrow mesenchymal stem cells-derived exosomes promote spinal cord injury repair through the miR-497-5p/TXNIP/NLRP3 axis.

机构信息

Department of Rehabilitation Medicine, Wuxi No.8 People's Hospital, Jiangsu Province, Wuxi City, 214000, China.

Department of Rehabilitation Medicine, Ezhou Central Hospital, Hubei Province, Ezhou City, 436000, China.

出版信息

J Mol Histol. 2024 Nov 29;56(1):16. doi: 10.1007/s10735-024-10289-z.

Abstract

Bone marrow mesenchymal stem cells (BMSCs) indicate a repairing prospect to treat spinal cord injury, a major traumatic disease. This study investigated the repair effect of bone marrow mesenchymal stem cell-derived exosomes (BMSC-Exos) on spinal cord injury. BMSCs were collected to extract BMSC-Exos which were identified by different means. The SCI model of rats was established, the motor behavior was scored by BBB field test, and the spinal cord tissues were separated and stained by HE, Nissl, and Tunel, respectively, as well as analyzed to measure inflammatory and oxidative stress responses. PC12 cells were co-cultured with Exos and analyzed by CCK-8 and flow cytometry to measure cell proliferation and apoptosis. BMSC-Exos improved SCI in rats with the recovery of motor function, alleviation of pathological conditions, and reduction of apoptosis, inflammatory responses, and oxidative stress. BMSC-Exos increased miR-497-5p expression, and miR-497-5p overexpression strengthened the protective effect of BMSC-Exos on SCI. miR-497-5p targeted inactivation of TXNIP/NLRP3 pathway. TXNIP saved the repair effect of miR-497-5p-carrying BMSC-Exos on SCI rats. miR-497-5p-carrying BMSC-Exos alleviated apoptosis and induced proliferation of HO-treated PC12 cells. BMSC-Exos promote SCI repair via the miR-497-5p/TXNIP/NLRP3 axis, which may be a target for alleviating SCI-associated nerve damage.

摘要

骨髓间充质干细胞(BMSCs)为治疗脊髓损伤这一重大创伤性疾病提供了修复前景。本研究探讨了骨髓间充质干细胞衍生的外泌体(BMSC-Exos)对脊髓损伤的修复作用。收集 BMSCs 提取 BMSC-Exos,通过不同方法进行鉴定。建立大鼠脊髓损伤模型,BBB 场测试评分大鼠运动行为,分别采用 HE、Nissl 和 Tunel 染色分离脊髓组织,并分析测量炎症和氧化应激反应。将 PC12 细胞与 Exos 共培养,通过 CCK-8 和流式细胞术分析测量细胞增殖和凋亡。BMSC-Exos 改善了大鼠脊髓损伤,恢复了运动功能,减轻了病理状况,减少了细胞凋亡、炎症反应和氧化应激。BMSC-Exos 增加了 miR-497-5p 的表达,miR-497-5p 的过表达增强了 BMSC-Exos 对 SCI 的保护作用。miR-497-5p 靶向 TXNIP/NLRP3 通路失活。TXNIP 挽救了 miR-497-5p 携带的 BMSC-Exos 对 SCI 大鼠的修复作用。miR-497-5p 携带的 BMSC-Exos 减轻了 HO 处理的 PC12 细胞的凋亡并诱导其增殖。BMSC-Exos 通过 miR-497-5p/TXNIP/NLRP3 轴促进 SCI 修复,这可能是减轻与 SCI 相关的神经损伤的一个靶点。

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