中国神经再生研究(英文版)

中国神经再生研究(英文版) ›› 2013, Vol. 8 ›› Issue (14): 1307-1315.doi: 10.3969/j.issn.1673-5374.2013.14.007

• 原著:脑损伤修复保护与再生 • 上一篇    下一篇

神经肽Y基因转染癫痫大鼠脑内的抗癫痫

  

  • 收稿日期:2012-08-20 修回日期:2013-04-24 出版日期:2013-05-15 发布日期:2013-05-15

Anti-epileptic effects of neuropeptide Y gene transfection into the rat brain

Changzheng Dong1, Wenqing Zhao1, 2, Wenling Li2, Peiyuan Lv3, Xiufang Dong4   

  1. 1 Faculty of Graduate Studies, Hebei Medical University, Shijiazhuang 050051, Hebei Province, China
    2 Department of Functional Neurosurgery, Hebei General Hospital, Shijiazhuang 050051, Hebei Province, China
    3 Department of Neurology, Hebei General Hospital, Shijiazhuang 050051, Hebei Province, China
    4 Department of Neurology, First Hospital of Xingtai, Xingtai 054000, Hebei Province, China
  • Received:2012-08-20 Revised:2013-04-24 Online:2013-05-15 Published:2013-05-15
  • Contact: Wenqing Zhao, Professor. Faculty of Graduate Studies, Hebei Medical University, Shijiazhuang 050051, Hebei Province, China; Department of Functional Neurosurgery, Hebei General Hospital, Shijiazhuang 050051, Hebei Province, China, promisingznd@gmail.com.
  • About author:Changzheng Dong☆, M.D., Attending Physician.

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摘要：

正常大鼠的脑组织中神经肽Y基因过表达，可以减轻红藻氨酸诱导大鼠癫痫的发作程度。实验以重组腺相关病毒为载体，将神经肽Y基因通过立体定向的方法转染到红藻氨酸诱发的癫痫大鼠脑内。结果显示，神经肽Y可以实现在癫痫脑内的基因过表达。基因转染后4周，脑电图显示，大鼠的癫痫发作程度明显被抑制，发作潜伏期明显延长；荧光定量PCR和western blot检测显示癫痫大鼠海马内N-甲基-D-天门冬氨酸受体亚单位NR1, NR2A, NR2B的mRNA和蛋白表达受到抑制。提示神经肽Y基因转染可通过下调N-甲基-D-天门冬氨酸受体的表达，发挥抗癫痫作用。

关键词: 神经再生, 基因治疗, 神经退行性变, 脑损伤, 腺相关病毒, 神经肽Y, 癫痫, N-甲基-D-天门冬氨酸受体, 红藻氨酸

Abstract:

Neuropeptide Y gene transfection into normal rat brain tissue can provide gene overexpression, which can attenuate the severity of kainic acid-induced seizures. In this study, a recombinant adeno-associated virus carrying the neuropeptide Y gene was transfected into brain tissue of rats with kainic acid-induced epilepsy through stereotactic methods. Following these transfections, we verified overexpression of the neuropeptide Y gene in the epileptic brain. Electroencephalograms showed that seizure severity was significantly inhibited and seizure latency was significantly prolonged up to 4 weeks after gene transfection. Moreover, quantitative fluorescent PCR and western blot assays revealed that the mRNA and protein expression of the N-methyl-D-aspartate receptor subunits NR1, NR2A, and NR2B was inhibited in the hippocampus of epileptic rats. These findings indicate that neuropeptide Y may inhibit seizures via down-regulation of the functional expression of N-methyl-D-aspartate receptors.

Key words: neural regeneration, brain injury, gene therapy, adeno-associated virus, neuropeptide Y, epilepsy, N-methyl-D-aspartate receptor, kainic acid, seizures, neuroregeneration