中国神经再生研究(英文版) ›› 2014, Vol. 9 ›› Issue (23): 2053-2058.doi: 10.4103/1673-5374.147930

• 原著:脑损伤修复保护与再生 • 上一篇    下一篇

人骨髓间充质干细胞移植减轻脑缺血大鼠轴突损伤

  

  • 收稿日期:2014-11-26 出版日期:2014-12-10 发布日期:2014-12-10

Human bone marrow mesenchymal stem cell transplantation attenuates axonal injury in stroke rats

Yi Xu 1, Shiwei Du 2, Xinguang Yu 1, Xiao Han 3, 4, Jincai Hou 3, 4, Hao Guo 3, 4   

  1. 1 Department of Neurosurgery, General Hospital of Chinese PLA, Beijing, China
    2 Department of Neurosurgery, General Hospital of Armed Police Forces, Beijing, China
    3 Xiyuan Hospital, China Academy of Chinese Medical Sciences, Institute of Basic Medical Sciences, Beijing, China
    4 Beijing Key Laboratory of Pharmacology of Chinese Materia Medica, Institute of Basic Medcal Sciences of Xuyuan Hospital, Beijing, China
  • Received:2014-11-26 Online:2014-12-10 Published:2014-12-10
  • Contact: Xinguang Yu, M.D., Department of Neurosurgery, General Hospital of Chinese PLA, Beijing 100853, China, strongxu2002@sina.com.

摘要:

研究报道人骨髓间充质干细胞移植可促进脑卒中后的神经功能恢复,但其机制不甚清楚。我们假设人骨髓间充质干细胞移植促进神经功能恢复的机制与其轴突及髓鞘保护作用相关。实验建立了大鼠大脑中动脉闭塞缺血/再灌注模型,发现模型大鼠可出现严重的轴突和髓鞘损伤。经股静脉移植人骨髓间充质干细胞治疗后,经行为学评估、脑梗塞检测和免疫荧光染色表明,轴突和髓鞘相关标志物-微管相关蛋白2、髓鞘碱性蛋白和生长相关蛋白43蛋白荧光反应的增强,脑梗塞区域减小,神经功能恢复。说明股静脉移植人骨髓间充质干细胞可促进脑缺血大鼠神经功能恢复,其机制与抑制脱髓鞘和轴突变性,促进轴突新生有关。

关键词: 神经再生, 缺血性脑卒中, 神经功能, 神经保护, 微管相关蛋白2, 髓鞘碱性蛋白, 生长相关蛋白43蛋白, 轴突, 髓鞘, 脱髓鞘, 轴突再生, 细胞外

Abstract:

Previous studies have shown that transplantation of human bone marrow mesenchymal stem cells promotes neural functional recovery after stroke, but the neurorestorative mechanisms remain largely unknown. We hypothesized that functional recovery of myelinated axons may be one of underlying mechanisms. In this study, an ischemia/reperfusion rat model was established using the middle cerebral artery occlusion method. Rats were used to test the hypothesis that intravenous transplantation of human bone marrow mesenchymal stem cells through the femoral vein could exert neuroprotective effects against cerebral ischemia via a mechanism associated with the ability to attenuate axonal injury. The results of behavioral tests, infarction volume analysis and immunohistochemistry showed that cerebral ischemia caused severe damage to the myelin sheath and axons. After rats were intravenously transplanted with human bone marrow mesenchymal stem cells, the levels of axon and myelin sheath-related proteins, including microtubule-associated protein 2, myelin basic protein, and growth-associated protein 43, were elevated, infarct volume was decreased and neural function was improved in cerebral ischemic rats. These findings suggest that intravenously transplanted human bone marrow mesenchymal stem cells promote neural function. Possible mechanisms underlying these beneficial effects include resistance to demyelination after cerebral ischemia, prevention of axonal degeneration, and promotion of axonal regeneration.

Key words: nerve regeneration, human bone marrow mesenchymal stem cells, ischemic stroke, neural function, neuroprotection, microtubule-associated protein 2, myelin basic protein, growth associated protein 43, neuraxon, myelin sheath, demyelination, axon regeneration, neural regeneration