中国组织工程研究

中国组织工程研究 ›› 2011, Vol. 15 ›› Issue (14): 2562-2566.doi: 10.3969/j.issn.1673-8225.2011.14.020

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

立体定向移植骨髓间充质干细胞改善血管性大鼠的学习记忆能力

李丽杰1，孔繁明2，张学斌2，王新平3，王世民3，唐  帆2，张文治4，苏  心4   

  1. 1天津医科大学研究生院，天津市   300070；天津市环湖医院，2病理科，3神经内科，4神经外科研究所细胞室，天津市 300060
  • 收稿日期:2010-10-11 修回日期:2010-11-15 出版日期:2011-04-02 发布日期:2013-11-02
  • 通讯作者: 王世民，教授，硕士生导师，天津市环湖医院神经内科，天津市 300060 wangxinpingtj@sina.com
  • 作者简介:李丽杰★，女，1983年生，河北省定兴县人，汉族，天津医科大学在读硕士，主要从事干细胞方面的研究。 976038027@qq.com
  • 基金资助:

    天津市卫生局科技基金支持项目,课题名称：骨髓间充质干细胞移植治疗血管性痴呆的实验研究。

Stereotactic transplantation of bone marrow mesenchymal stem cells for learning and memory ability of vascular rats

Li Li-jie1, Kong Fan-ming2, Zhang Xue-bin2, Wang Xin-ping3, Wang Shi-min3, Tang Fan2, Zhang Wen-zhi4, Su Xin4   

  1. 1Postgraduate College, Tianjin Medical University, Tianjin  300070, China; 2Department of Pathology, 3Department of Neurology, 4Cell Room of Institute of Neurosurgery, Huanhu Hospital, Tianjin  300060, China
  • Received:2010-10-11 Revised:2010-11-15 Online:2011-04-02 Published:2013-11-02
  • Contact: Wang Shi-min, Professor, Master’s supervisor, Department of Neurology, Huanhu Hospital, Tianjin 300060, China wangxinpingtj@sina.com
  • About author:Li Li-jie★, Studying for master’s degree, Postgraduate College, Tianjin Medical University, Tianjin 300070, China 976038027@qq.com
  • Supported by:

    Science and Technology Foundation of Tianjin Health Bureau*

PDF

466

被引次数

6

摘要：

背景：大量的实验证明将骨髓间充质干细胞移植到复制的中枢神经系统疾病大鼠模型后，能迁移到损伤部位，表达神经细胞的潜在特性并且提高神经功能。
目的：验证骨髓间充质干细胞对拟人类血管性痴呆模型大鼠学习记忆障碍的改善作用。
方法：分离SD大鼠骨髓间充质干细胞，于细胞移植前掺入10 mg/L的BrdU进行标记。建立Wistar大鼠血管性痴呆样学习记忆障碍动物模型，随机分为模型组、假手术组与移植组。移植组致伤后第14天，通过立体定向途径移植骨髓间充质干细胞到大鼠海马，假手术组给予等量生理盐水，模型组大鼠不做处理。采用Morris水迷宫检测大鼠空间学习记忆能力。损伤后第90天处死大鼠，观察海马组织有无Brdu+神经元特异性烯醇化酶、Brdu+胶质纤维酸性蛋白免疫组织化学双染阳性细胞，并且观察从侧脑室到海马是否存在神经元前体细胞的标志Doublecortin (DCX)吻侧迁移流。
结果与结论：①移植组大鼠采用Morris水迷宫检测大鼠空间学习记忆能力逃避潜伏期及跨越平台次数优于模型组及假手术组(P < 0.05)。②移植组大鼠海马组织及其周围可见免疫组织化学双染阳性细胞，但未见从侧脑室到海马关于神经元前体细胞的标志Doublecortin (DCX)吻侧迁移流。结果提示，骨髓间充质干细胞移植可以促进脑损伤大鼠的神经功能的恢复，其机制可能与移植细胞分化为神经元样和神经胶质细胞样细胞，并分泌或促进宿主分泌神经营养因子有关。

关键词: 血管性痴呆, 骨髓间充质干细胞, Morris水迷宫, 学习记忆障碍, 大鼠

Abstract:

BACKGROUND: The key of stem cells for treating nervous tissue injury is the transplantation of stem cells that have regeneration capacity. The damaged neurons are restored by multiple action mechanisms, which recover the nervous function.
OBJECTIVE: To explore the effects of bone marrow mesenchymal stem cells (BMSCs) on learning and memory disorders of vascular dementia model rats.
METHODS: BMSCs were separated with density gradient centrifugation and screening the cells adherent to the plastic surface.
10 mg/L BrdU was used to label before cell transplantation. Adult female Wistar rats were used to establish vascular dementia rat models by Permanent bilateral carotid artery ligation, and they were then randomly divided into control group, saline group and transplantation group. In the transplantation group, BMSCs were transplanted into the damaged spinal cord by stereotaxis at day 7 following damage. In the saline group, an equal volume of saline was utilized. In the control group, the rats were left intact. In the transplantation group, BMSCs were transplanted into the damaged Hippocampus by stereotaxis at day 14 following damage. In the saline group, an equal volume of saline was utilized. In the control group, the rats were left intact. Spatial learning and memory was detected by the Morris Water maze. Rats were sacrificed at day 90. Brdu+neuron specific enolase, Brdu+glial fibrillary acidic protein (GFAP) immunohistochemistry double-staining cells, and the migration of Doublecortin (DCX, the marker of N Ps) from the subventricular zone to the damaged hippocampus were observed.
RESULTS AND CONCLUSION: ①Spatial learning and memory in rats (escape latency and the number of cross platform) was better in the transplantation group than in the control group (P < 0.05). No significant difference was determined in the control group and the saline group. ②Double-staining cells of immunohistochemistry could be found at the center of damage site and the surrounding site in rats of the transplantation group. Results indicated that BMSC transplantation can improve the recovery of nervous function of rats with spinal cord injury. Its mechanism may be correlated with the differentiation of transplanted cells into neuron-like and glial cell-like cells, secretion or promoting secretion of neurotrophic factors in host.

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