中国神经再生研究(英文版)

中国神经再生研究(英文版) ›› 2014, Vol. 9 ›› Issue (18): 1665-1671.doi: 10.4103/1673-5374.141801

• 原著:脊髓损伤修复保护与再生 • 上一篇    下一篇

骨髓间充质干细胞通过促进轴突生长和抗自噬修复脊髓缺血再灌注损伤

  

  • 收稿日期:2014-07-14 出版日期:2014-09-26 发布日期:2014-09-26
  • 基金资助:

    国家自然基金项目（30972153）；吉林省科技发展计划项目(200905183), 吉林省卫生厅科研课题(2008Z041)

Bone marrow mesenchymal stem cells repair spinal cord ischemia/reperfusion injury by promoting axonal growth and anti-autophagy

Fei Yin 1, Chunyang Meng 1, Rifeng Lu 2, Lei Li 1, Ying Zhang 2, Hao Chen 1, Yonggang Qin 2, Li Guo 2   

  1. 1 Department of Orthopedics, China-Japan Union Hospital, Jilin University, Changchun, Jilin Province, China
    2 Department of Toxicology, School of Public Health, Jilin University, Changchun, Jilin Province, China
  • Received:2014-07-14 Online:2014-09-26 Published:2014-09-26
  • Contact: Li Guo, Ph.D., Department of Toxicology, School of Public Health, Jilin University, Changchun 130021, Jilin Province, China, gli@jlu.edu.cn.
  • Supported by:

    This study was supported by the National Natural Science Foundation of China, No. 30972153; the Science and Technology Development Program of Jilin Provincial Science and Technology Department in China, No. 200905183; and the Scientific Research Foundation of Jilin Department of Health of China, No. 2008Z041.

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摘要：

作者既往研究曾发现，将骨髓间充质干细胞移植进脊髓缺血再灌注损伤大鼠体内，在受损脊髓中可分化为神经元和星形胶质细胞，并通过抗凋亡作用修复脊髓缺血再灌注损伤，但其机制不明确。此次实验将骨髓间充质干细胞培养扩增后，经眼眶球后静脉注射移植至脊髓缺血再灌注损伤大鼠体内。免疫组化和免疫荧光显示，脊髓缺血再灌注损伤大鼠脊髓组织中轴突再生标志物生长相关蛋白43和中枢神经系统损伤标志物微管相关蛋白2表达显著增加，自噬标志物微管相关蛋白轻链3B和Beclin1表达减少。Western blot也显示，脊髓缺血再灌注损伤大鼠脊髓组织中生长相关蛋白43表达增加，自噬标志物微管相关蛋白轻链3B和Beclin1表达减少，还发现神经丝蛋白H的表达增加。因此，作者认为骨髓间充质干细胞移植能促进神经元轴突的生长、再生并有抗自噬作用，这可能是骨髓间充质干细胞修复脊髓缺血再灌注损伤的机制之一。

关键词: 神经再生, 骨髓间充质干细胞, 脊髓缺血再灌注损伤, 轴突生长, 自噬, 修复, NSFC grant

Abstract:

Bone marrow mesenchymal stem cells can differentiate into neurons and astrocytes after transplantation in the spinal cord of rats with ischemia/reperfusion injury. Although bone marrow mesenchymal stem cells are known to protect against spinal cord ischemia/reperfusion injury through anti-apoptotic effects, the precise mechanisms remain unclear. In the present study, bone marrow mesenchymal stem cells were cultured and proliferated, then transplanted into rats with ischemia/reperfusion injury via retro-orbital injection. Immunohistochemistry and immunofluorescence with subsequent quantification revealed that the expression of the axonal regeneration marker, growth associated protein-43, and the neuronal marker, microtubule-associated protein 2, significantly increased in rats with bone marrow mesenchymal stem cell transplantation compared with those in rats with spinal cord ischemia/reperfusion injury. Furthermore, the expression of the autophagy marker, microtubule-associated protein light chain 3B, and Beclin 1, was significantly reduced in rats with the bone marrow mesenchymal stem cell transplantation compared with those in rats with spinal cord ischemia/reperfusion injury. Western blot analysis showed that the expression of growth associated protein-43 and neurofilament-H increased but light chain 3B and Beclin 1 decreased in rats with the bone marrow mesenchymal stem cell transplantation. Our results therefore suggest that bone marrow mesenchymal stem cell transplantation promotes neurite growth and regeneration and prevents autophagy. These responses may likely be mechanisms underlying the protective effect of bone marrow mesenchymal stem cells against spinal cord ischemia/reperfusion injury.

Key words: nerve regeneration, bone marrow mesenchymal stem cells, spinal cord ischemia/reperfusion injury, axonal growth, autophagy, repair, NSFC grant, neural regeneration