中国组织工程研究

中国组织工程研究 ›› 2012, Vol. 16 ›› Issue (6): 1003-1006.doi: 10.3969/j.issn.1673-8225.2012.06.012

• 干细胞培养与分化 stem cell culture and differentiation • 上一篇    下一篇

离子型谷氨酸受体拮抗剂MK-801浓度与全脑缺血再灌注大鼠海马内源性神经干细胞的增殖**★

袁国艳1，任铭新2，郭义威2，周  立2   

  1. 1新乡医学院第一附属医院神经外科，河南省卫辉市   453100；2新乡医学院人体解剖学教研室，河南省新乡市  453003
  • 收稿日期:2011-07-01 修回日期:2011-10-29 出版日期:2012-02-05 发布日期:2012-02-05
  • 通讯作者: 任铭新，硕士，讲师，新乡医学院人体解剖学教研室，河南省新乡市 453003 hnlyrmx@163.com.
  • 作者简介:袁国艳★，女，1980年生，河南省开封市人，汉族，2003年新乡医学院毕业，硕士，主治医师，主要从事神经外科脑损伤修复研究。yuanguoyan2001@163.com
  • 基金资助:

    2009年度新乡医学院第七批省级重点学科开放课题资助项目(ZD200923)；2011年新乡医学院重点研究领域招标课题项目(ZD2011-14)。

Effect of ionotropic glutamate receptor antagonists MK-801 on the proliferation of endogenous neural stem cells in rats with global cerebral ischemia-reperfusion injury

Yuan Guo-yan1, Ren Ming-xin2, Guo Yi-wei2, Zhou Li2   

  1. 1Department of Neurosurgery, the First Affiliated Hospital of Xinxiang Medical College, Weihui  453100, Henan Province, China; 2Department of Anatomy, Xinxiang Medical College, Xinxiang  453003, Henan Province, China
  • Received:2011-07-01 Revised:2011-10-29 Online:2012-02-05 Published:2012-02-05
  • Contact: Ren Ming-xin, Master, Lecturer. Department of Anatomy, Xinxiang Medical College, Xinxiang 453003, Henan Province, China hnlyrmx@163.com
  • About author:Yuan Guo-yan★, Master, Attending physician, Department of Neurosurgery, the First Affiliated Hospital of Xinxiang Medical College, Weihui 453100, Henan Province, China yuanguoyan2001@163.com
  • Supported by:

     the Seventh Installment of Provincial Key Disciplines Open Issues of Xinxiang Medical College in 2009, No. ZD200923*; Tender Subject of Key Research Areas of Xinxinag Medical College in 2011, No.ZD2011-14*

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摘要：

背景：脑缺血再灌注后，过度释放的兴奋性氨基酸可通过N-甲基-D-天冬氨酸(NMDA)受体激活内源性神经干细胞，促使其增殖、分化，修复神经细胞，但同时也导致细胞内钙离子超载，引起神经细胞的损伤。
目的：观察NMDA受体拮抗剂MK-801浓度对脑缺血再灌注大鼠海马内源性神经干细胞增殖的影响。
方法：SD大鼠随机分为正常对照组、手术对照组及MK-801 0.2，0.4，0.6，0.8，1.0，1.2 mg/kg组。除正常对照组外，大鼠首先进行侧脑室插管，3 d后进行4条血管阻断方法制备大鼠全脑缺血再灌注模型。在模型制作前30 min按照不同浓度侧脑室注射MK-801。正常对照组和手术对照组侧脑室注射同剂量的生理盐水。免疫组织化学、RT-PCR技术检测各组脑海马nestin阳性细胞及其mRNA表达。
结果与结论：MK-801浓度在0.8 mg/kg以下时，用药组大鼠脑海马nestin mRNA及蛋白的表达与手术对照组差异无显著性意义(P > 0.05)，呈现高表达；当MK-801浓度达到0.8 mg/kg时，与手术对照组相比，用药组大鼠脑海马nestin基因及蛋白的表达明显下降(P < 0.05)，并随浓度的增高呈递减趋势。提示MK-801在浓度为0.6 mg/kg时，即可抑制钙超载保护神经元，又有良好的刺激神经干细胞增殖作用。
关键词：离子型谷氨酸受体拮抗剂；脑缺血；再灌注；神经干细胞；MK-801
doi:10.3969/j.issn.1673-8225.2012.06.012

关键词: 离子型谷氨酸受体拮抗剂, 脑缺血, 再灌注, 神经干细胞, MK-801

Abstract:

BACKGROUND: After cerebral ischemia-reperfusion, excessive excitatory amino acids can activate endogenous neural stem cells (NSCs) through N-methyl-D-aspartic acid (NMDA) receptor and can repair nerve cells by the proliferation and differentiation of endogenous NSCs but damage nerve cells by intracellular calcium overload at the same time.
OBJECTIVE: To study the effect of NMDA receptor antagonist MK-801 on the proliferation of endogenous NSCs of global cerebral ischemia-reperfusion rat hippocampus.
METHODS: The SD rats were divided into control group, operation group and different concentrations of MK-801 group (0.2, 0.4, 0.6, 0.8, 1.0, 1.2 mg/kg). The rats were first treated with lateral ventricle intubation, and 3 days later, four-vessel occlusion was used to establish global cerebral ischemia-reperfusion model, except the control group. Different doses of MK-801 were intracerebrally ventricularly injected at 30 minutes before cerebral ischemia. The same concentration of normal saline was used in control group and operation group. Immunohistochemistry and RT-PCR technique were used to detect nestin positive cells and mRNA level expression.
RESULTS AND CONCLUSION: When the concentration of MK-801 was under 0.8 mg/kg, the protein and mRNA expression of nestin was high and there was no difference between MK-801 group and operation group (P > 0.05). When the concentration of MK-801 was equal to 0.8 mg/kg, the expression of nestin gene and protein was decreased significantly with MK-801 increasing (P < 0.05). MK-801 can not only inhibit calcium overload but also has good effect on stimulating neural stem cell proliferation at the concentration of 0.6 mg/kg.

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