强啡肽致大鼠脊髓损伤与谷氨酸能神经功能关系的研究  

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

作　　者：李富春[1,2] 左萍萍[1,2] 胡文辉 刘娜[1,2] 任民峰[1,2] 

机构地区：[1]中国医学科学院基础医学院 [2]中国协和医科大学药理教研室

出　　处：《中国康复理论与实践》1997年第1期6-9,共4页Chinese Journal of Rehabilitation Theory and Practice

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。篒ntrathecal (i. t. )administration of K opioid dynorphin A (l -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 (l-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 l0-6 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 (l-17 ) at physiological dosage may be rnediated by presynaptic K opioid receptor through the inhibition of Ca2+ influx and L-Glu release;but dynA (l-l7 )enhanced L-Glu release through a non-opioid pathway and induced hindlimb paralysis at high neurotoxic dosage.

关 键 词：脊髓损伤 强啡肽 谷氨酸释放 

分 类 号：R651.202[医药卫生—外科学]