中国神经再生研究(英文版)

中国神经再生研究(英文版) ›› 2023, Vol. 18 ›› Issue (6): 1293-1299.doi: 10.4103/1673-5374.357900

• 原著:脑损伤修复保护与再生 • 上一篇    下一篇

运动训练联合骨髓间充质干细胞来源外泌体减少神经元凋亡和轴突重塑具有协同作用

  

  • 出版日期:2023-06-15 发布日期:2023-01-05
  • 基金资助:
    国家自然科学基金项目（81772452），福建省科技创新联合基金项目（2020Y9065），福建自然科学创新专项基金项目（2016B014），福建省自然科学基金项目（2019J01160）

Treadmill exercise exerts a synergistic effect with bone marrow mesenchymal stem cell-derived exosomes on neuronal apoptosis and synaptic-axonal remodeling 

Xin-Hong Jiang1, 2, 3, #, Hang-Feng Li4, #, Man-Li Chen2, 3, 5, Yi-Xian Zhang1, 2, 3, Hong-Bin Chen2, 3, 5, Rong-Hua Chen2, 3, 5, Ying-Chun Xiao2, 3, 5, Nan Liu1, 2, 3, 5, *#br#   

  1. 1Department of Rehabilitation, Fujian Medical University Union Hospital, Fuzhou, Fujian Province, China;  2Fujian Institute of Cerebrovascular Disease, Fuzhou, Fujian Province, China;  3Key Laboratory of Brain Aging and Neurodegenerative Diseases, Fujian Key Laboratory of Molecular Neurology, Fujian Medical University, Fuzhou, Fujian Province, China;  4Department of Neurology, Longyan First Hospital of Fujian Medical University, Longyan, Fujian Province, China;  5Department of Neurology, Fujian Medical University Union Hospital, Fuzhou, Fujian Province, China
  • Online:2023-06-15 Published:2023-01-05
  • Contact: Nan Liu, MD, xieheliunan1984@sina.com.
  • Supported by:
    This work was supported by the National Natural Science Foundation of China, No. 81772452 (to NL), the Fujian Province Joint Funds for the Innovation of Science and Technology, No. 2020Y9065 (to NL), Fujian Province Special Foundation for Natural Science Innovation Project, No. 2016B014  (to NL), and the Natural Science Foundation of Fujian Province, No. 2019J01160 (to XHJ).

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摘要：

运动训练和间充质干细胞移植都是目前脑缺血治疗的切实有效方法,但两者是否存在协同作用仍不明确。实验以大脑中动脉闭塞2h再灌注24h建立永久性大脑中动脉闭塞缺血再灌注损伤大鼠模型后，尾静脉骨髓注射间充质干细胞来源的外泌体，并给予其连续14d的跑步机运动训练。行为学、组织病理学和免疫组化检测结果显示，联合治疗的大鼠脑组织神经元凋亡明显减少，脑梗死体积缩小，突触形成和轴突再生增殖，神经功能显著恢复，两者联合治疗的效果明显优于运动训练或骨髓间充质干细胞来源的外泌体单一治疗。进一步研究发现，其作用机制在于活化JNK1/c-Jun信号通路，进而调节神经元凋亡和突触-轴突重塑。以上结果表明运动训练可能与骨髓间充质干细胞来源的外泌体发挥协同作用，该作用的发挥可能与JNK1/c-Jun信号通路活化有关。这项研究为运动训练联合骨髓间充质干细胞来源的外泌体治疗缺血性脑血管病的临床应用提供了新的依据。

https://orcid.org/0000-0003-2901-3721 (Nan Liu); https://orcid.org/0000-0002-3695-5488 (Xin-Hong Jiang)

关键词: 运动训练, 骨髓间充质干细胞, 外泌体, JNK1, c-Jun, 缺血性脑卒中, 细胞凋亡, 突触形成, 轴突再生, 功能重塑

Abstract: Treadmill exercise and mesenchymal stem cell transplantation are both practical and effective methods for the treatment of cerebral ischemia. However, whether there is a synergistic effect between the two remains unclear. In this study, we established rat models of ischemia/reperfusion injury by occlusion of the middle cerebral artery for 2 hours and reperfusion for 24 hours. Rat models were perfused with bone marrow mesenchymal stem cell-derived exosomes (MSC-exos) via the tail vein and underwent 14 successive days of treadmill exercise. Neurological assessment, histopathology, and immunohistochemistry results revealed decreased neuronal apoptosis and cerebral infarct volume, evident synaptic formation and axonal regeneration, and remarkably recovered neurological function in rats subjected to treadmill exercise and MSC-exos treatment. These effects were superior to those in rats subjected to treadmill exercise or MSC-exos treatment alone. Mechanistically, further investigation revealed that the activation of JNK1/c-Jun signaling pathways regulated neuronal apoptosis and synaptic-axonal remodeling. These findings suggest that treadmill exercise may exhibit a synergistic effect with MSC-exos treatment, which may be related to activation of the JNK1/c-Jun signaling pathway. This study provides novel theoretical evidence for the clinical application of treadmill exercise combined with MSC-exos treatment for ischemic cerebrovascular disease. 

Key words: apoptosis, axonal regeneration, c-Jun, exosomes, functional remodeling, ischemic stroke, JNK1, mesenchymal stem cells, synaptic formation, treadmill exercise