中国组织工程研究

中国组织工程研究 ›› 2010, Vol. 14 ›› Issue (40): 7474-7478.doi: 10.3969/j.issn.1673-8225.2010.40.014

• 干细胞移植 stem cell transplantation • 上一篇    下一篇

骨髓间充质干细胞移植及生长相关蛋白43表达在脑修复中的作用

王  娜1，曹  文2，刘广义3   

  1. 1青岛市骨伤科医院脊柱二科，山东省青岛市 266021；2青岛大学医学院附属医院放射科，山东省青岛市 266003；3青岛大学医学院附属医院脑血管病研究所，山东省青岛市  266003
  • 出版日期:2010-10-01 发布日期:2010-10-01
  • 通讯作者: 刘广义，青岛大学医学院附属医院脑血管病研究所，山东省青岛市 266003 lgy1658@yahoo.com.cn
  • 作者简介:王娜，女，1982年生，山东省青岛市人，汉族，2007年中国医科大学毕业，护师，主要从事神经康复方面的研究。 HAO1335686@yahoo.com.cn

Effects of bone marrow mesenchymal stem cells transplantation and growth associated protein-43 expression in brain repair

Wang Na1, Cao Wen2, Liu Guang-yi3   

  1. 1 Second Department of Spinal Column, Qingdao Orthopaedics and Traumatology Hospital, Qingdao  266021, Shandong Province, China; 2 X-ray Room, Affiliated Hospital of Qingdao University Medical College, Qingdao 266003, Shandong Province, China; 3 Institute of Cerebrovascular Diseases, Affiliated Hospital of Qingdao University Medical College, Qingdao  266003, Shandong Province, China
  • Online:2010-10-01 Published:2010-10-01
  • Contact: Liu Guang-yi, Institute of Cerebrovascular Diseases, Affiliated Hospital of Qingdao University Medical College, Qingdao 266003, Shandong Province, China lgy1658@yahoo.com.cn
  • About author:Wang Na, Nurse practitioner, Second Department of Spinal Column, Qingdao Orthopaedics and Traumatology Hospital, Qingdao 266021, Shandong Province, China HAO1335686@yahoo.com.cn

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摘要：

背景：研究证实骨髓间充质干细胞移植能够促进脑功能恢复，并对大鼠脑皮质及海马结构损伤具有修复作用，可能与细胞的自身代偿以及神经生长递质的参与有关，也可能是由于神经应激性损伤刺激靶组织细胞分泌各种神经因子的表达有关。
目的：从细胞生物学的角度，观察大鼠脑缺血损伤后骨髓间充质干细胞移植对神经再生及脑的修复作用。
方法：参考改良Nagasawa法建立大脑中动脉闭塞再灌注模型后，实施骨髓间充质干细胞移植，并分别进行跑台运动训练和水迷宫康复训练，进行神经功能评分及学习记忆评分。采用TUNEL法检测脑皮质区及海马区凋亡神经元的表达以及免疫组化技术检测生长相关蛋白43蛋白在两区的表达变化。
结果与结论：移植组16 h移植骨髓间充质干细胞在皮质区及海马CA1区表达明显增加；7 d细胞表达达高峰，分化细胞明显增加。移植后运动训练7，19，21 d移植组mNSS评分低于模型组(P均< 0.01)；移植组大鼠水迷宫试验平台潜伏期的时间较模型组明显缩短(P < 0.05)；移植组大鼠穿越平台次数较模型组增多(P < 0.05)；缺血再灌注24 h凋亡细胞达高峰，3 d梗死体积测量为最大值；再灌注19 d生长相关蛋白43达高峰。提示大鼠脑缺血损伤介导了神经功能缺损，骨髓间充质干细胞移植促进了神经再生，生长相关蛋白43表达上调抑制神经元凋亡，进一步促进了脑梗死灶的修复。

关键词: 生长相关蛋白43, 脑缺血, 骨髓间充质干细胞, 细胞移植, 神经再生, 脑修复

Abstract:

BACKGROUND: The bone marrow stromal cells transplantation can promote rat brain functional recovery, and have reparation function in cortex and hippocampal structure injury. These may be associated with cell self-compensation and nerve growth media, or because nervous irritability injury stimulates target tissue cells to secrete various nerve factor expression.
OBJECTIVE: To observe the role of bone marrow mesenchymal stem cells (BMSCs) transplantation on cerebral recovery and nerve regeneration after cerebral ischemia injury in rats from the angle of cell biology.
METHODS: In accordance with modified Nagasawa’s method, the middle cerebral artery occlusion/reperfusion (MCAO/R) model was established. BMSCs transplantation was performed, followed by running machine sports training and water maze test. Neurobehavioral scores, learning and memory scores were observed. TUNEL method was used to detect the expression of apoptotic neurons in cortex region and in hippocampus region, and immunohistochemical technique was utilized to determine expression change of growth associated protein-43 protein in two districts.
RESULTS AND CONCLUSION: In transplantation group, BMSCs expression was significantly increased in the cortical area and hippocampal CA1 region at 16 hours, peaked at 7 days, and the number of differentiated cells was significantly increased. Following transplantation, modified neurological severity score was lower in the transplantation group at 7, 19 and 21 days compared with model group (P < 0.01). The time of platform latency was obviously shortened in the water maze test in the transplantation group compared with model group (P < 0.05). The number of times of crossing the platform was greater in the transplantation group compared with model group (P < 0.05). The number of apoptotic cells peaked at 24 hours following ischemia/reperfusion injury. At 3 days, infarct volume was maximal. At 19 days following reperfusion, growth associated protein-43 expression peaked. These indicate that cerebral ischemia mediated neurologic impairment in rats. BMSCs transplantation contributed to neural regeneration. Up-regulation of growth associated protein-43 expression suppressed neuronal apoptosis, and further promoted the repair of cerebral infarction.

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