中国组织工程研究 ›› 2011, Vol. 15 ›› Issue (40): 7505-7510.doi: 10.3969/j.issn.1673-8225.2011.40.022

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

神经干细胞移植联用神经节苷脂对脑损伤大鼠神经学功能恢复的影响

李红星1,苑国富1,金耀东2,王  静3,赵宗茂4   

  1. 徐水县人民医院,1神经外科,2急诊科,3药剂科,河北省徐水县  072550;4河北医科大学附属医院第二医院神经外科,河北省石家庄市  050000
  • 收稿日期:2010-10-28 修回日期:2010-12-16 出版日期:2011-10-01 发布日期:2011-10-01
  • 通讯作者: 苑国富,硕士,主治医师,徐水县人民医院神经外科,河北省徐水县072550
  • 作者简介:李红星,男,1975年,河北省徐水县人,汉族,2007年河北大学医学部毕业,主治医师,主要从事颅脑损伤的研究。 Lhxwj123@sina.com
  • 基金资助:

    河北省医学科学研究重点课题计划(20110598)。

Effects of ganglioside combined with neural stem cells transplantation on the neurologic function of rats with traumatic brain injury

Li Hong-xing1, Yuan Guo-fu1, Jin Yao-dong2, Wang Jing3, Zhao Zong-mao4   

  1. 1Department of Neurosurgery, 2Department of Emergency, 3Department of Phanrmacy, People's Hospital, Xushui  072550, Hebei Province, China; 4Department of Neurosurgery, Second Affiliated Hospital of Hebei Medical University Shijiazhuang  050000, Hebei Province, China
  • Received:2010-10-28 Revised:2010-12-16 Online:2011-10-01 Published:2011-10-01
  • Contact: Yuan Guo-fu, Master, Attending physician, Department of Neurosurgery, Xushui People's Hospital, Xushui 072550, Hebei Province, China sheibobobo@163.com
  • About author:Li Hong-xing, Attending physician, Department of Neurosurgery, Xushui People's Hospital, Xushui 072550, Hebei Province, China Lhxwj123@sina.com
  • Supported by:

    Hebei Provincial Medical Research Project, No.20110598*

摘要:

背景:研究表明, 神经节苷脂(GM1)通过激活神经营养因子,抑制毒性产物对神经元的损害,并且能够减少兴奋性氨基酸所引起的神经细胞的死亡起到促进神经细胞修复的作用。
目的:神经干细胞移植同时应用GM1,观察两者对脑损伤大鼠恢复的影响。
方法:取健康Wistar大鼠制成重型液压颅脑损伤模型,随机分成3组:损伤组(培养液移植组),神经干细胞移植组,神经干细胞+GM1组。脑损伤后4 d用RT-PCR、Western Blot检测脑组织中AQP4基因表达和蛋白合成的变化,并于脑损伤后24 h,3 d及伤后1,2,3,4 周行动物神经学缺损评分,在脑损伤后21~28 d进行Morris水迷宫试验。4周后处死大鼠行免疫组化、苏木精-伊红染色组织学观察。
结果及结论:脑损伤后4 d脑损伤周围组织AQP4及其mRNA的表达损伤组高于神经干细胞移植组,神经干细胞移植组高于神经干细胞+ GM1组(P < 0.05);移植后1,2,3,4 周,大鼠神经学缺损评分及水迷宫测试结果显示,神经干细胞移植可明显改善重型颅脑损伤后大鼠的神经功能,联合应用GM1有协同效果。移植4周后苏木精-伊红染色神经干细胞+ GM1组出现典型的神经细胞样形态学改变且软化灶消失。免疫组化染色结果显示大鼠损伤灶脑组织中的BrdU阳性细胞数神经干细胞+GM1组高于NSCs移植组和损伤组。提示神经干细胞移植可明显改善重型颅脑损伤后大鼠的神经学功能,联合应用GM1有协同效果。

关键词: 脑损伤, 神经干细胞, 移植, 神经节苷脂, 大鼠

Abstract:

BACKGROUND: Ganglioside (GM1), through activation of neurotrophic factors, inhibits the damage of toxic products to neurons and reduces nerve cell death induced by excitatory amino acids to play a role in nerve cell repair.
OBJECTIVE: To investigate the effect of neural stem cells (NSCs) transplantation and GM1 on traumatic brain injury (TBI).
METHODS: Healthy Wistar rats were divided randomly into three groups: TBI group; NSCs transplantation group; NSCs transplantation+ GM1 group. AQP4 mRNA and AQP4 expressions were determined by RT-PCR and Western Blot at 4 day after TBI. The neurological defect scores were determined 24 hours, 3 days and 1, 2, 3, 4 weeks after TBI. The Morris water maze test was tested on days 21-28 after TBI. The immunohistochemistry and pathology changes were checked after 4 weeks.
RESULTS AND CONCLUSION: The expressions of AQP4 mRNA and AQP4 were highest in the TBI group, higher in the NSCs transplantation group and lowest in the NSCs transplantation+ GM1 group (P < 0.05). At 1, 2, 3 and 4 weeks after TBI, the neurological defect scores were lower in the NSCs transplantation group than those in the TBI group (P < 0.05), and significantly lower in the NSCs transplantation+GM1 group than those in the TBI group (P < 0.01); The average time of escape latency was gradually decreased in each group. However, from the 3rd to 5th day, it was much shorter in the NSCs transplantation+GM1 group than in the TBI group (P < 0.01) and shorter in the NSCs transplantation+GM1 group than in NSCs transplantation group (P < 0.05). In addition, the frequency platform passing in the NSCs transplantation+GM1 group and the percentage of swimming distance traveled in the previous target quadrant was significantly greater than those of the TBI group and NSCs transplantation group. The number of neurons in the NSCs transplantation+GM1 group was higher than that in the NSCs transplantation group and TBI group (P < 0.05). GM1 combined with neural stem cells transplantation can significantly improve the neurological function in the rats with TBI. 

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