《中国康复理论与实践》

《中国康复理论与实践》 ›› 1997, Vol. 3 ›› Issue (01): 6-9.

• 理论与实践 • 上一篇    下一篇

强啡肽致大鼠脊髓损伤与谷氨酸能神经功能关系的研究

李富春; 左萍萍; 胡文辉; 刘娜; 任民峰   

  1. 中国医学科学院基础医学院;中国协和医科大学药理教研室
  • 收稿日期:1996-05-07 出版日期:1997-03-25 发布日期:1997-03-25

Glutamate Involved in Rats with Spinal Cord Injury Induced by Dynorphin A (1-17)

Li Fuchun,Zuo Pingping,Hu Wenhui,et al.   

  1. Chinese Journal of Rehabilitation Theory & Practice.-1997,3(1):6～9
  • Received:1996-05-07 Published:1997-03-25 Online:1997-03-25

PDF (PC)

被引次数

5

摘要： 为研究脊髓损伤及继发损伤的机理，本实验建立了蛛网膜下腔注射强啡肽A（DynA）致大鼠脊髓损伤的模型。发现兴奋性氨基酸谷氨酸（Glu）受体的亚型-N-甲基-D-天冬氨酸（NMDA）受体拮抗剂DL－2-氨基-5磷酰戊酸（APV）具有对抗DynA致瘫的显著疗效。又进一步观察了不同浓度DynA（1－17）对离体大鼠脊髓片H－Glu释放的影响。发现高钾去极化引起脊髓片释放3H-Glu是一个Ca2+依赖的过程。低浓度DynA（1－17）10-8mol／L，抑制3H－Glu释放．而10-6mol／L。显著增加释放，无致瘫作用的K阿片受体激动剂U50，488H于上述浓度均明显抑制3H－Glu的释放。结果提示，小剂量DynA（1－17）可能通过降低交触前Ca2+内流抑制Glu释放而镇痛，大剂量DynA（1-17）则通过促进Glu释放并作用于NMDA受体而引起神经损伤。

关键词: 脊髓损伤, 强啡肽, 谷氨酸释放, NMDA受体

Abstract: Intrathecal (I. T.)administration of K opioid dynorphin A (1-17) is used as a model of neurological dysfunction which lnvolved in spinal cord injury and secondary affection according to several previous reports. 5-amlno-2-phosphoveroleric acid (APV ), an NMDA receptor antagonist, can significantlly prevent the hindlimb paralysis in rats produced by I. T. dynorPhin A (1-17). To further investigate the mechanisms, we establis11 a nlodel of [3H]L,-Glu release in rats spinal slices influenced by dynorphin A (dynA ) (1-17). [3H]L-Glu release evoked by high [K+] (5Ommol/L,)is a Ca2+-dependent process. DynA (1-17) slgnificantly inhibited [3H]L,-Glu release at 1O-8mol/L,, but very significantly enhanced [3H]L-Glu release at 10-6 mol /L. The synthetic k agonist U50, 488H, which has no neurotoxic effect, inhibited [3H]L-Glu release at both high and low concentrations and did not have any enhancing effect. The results suggest that the analgesic effect of dynA (1-17) at physiological dosage may be rnediated by presynaptic K opioid receptor through the inhibition of Ca2+ influx and L-Glu release;but dynA (1-l7)enhanced L-Glu release through a non-opioid pathway and induced hindlimb paralysis at high neurotoxic dosage.

Key words: spinal cord injury, dynorphin, glutamate release, NMDA receptor