强啡肽A（1－17）致大鼠脊髓损伤

为研究脊髓损伤及继发性损伤的发病机理及其治疗方法，建立了蛛网膜下腔注射强啡肽Ａ（ＤｙｎＡ）致大鼠脊髓损伤动物模型。发现内源性ＤｙｎＡ（１－１７）的氨基端酪氨酸与竣基端的氨基酸残基在致脊髓损伤中都是重要的：Ｎ－甲基－Ｄ－天冬氨酸受体拮抗剂ＤＬ－２－氨基－５－胯酰戊酸（ＡＰＶ），犬尿氨酸及ＭＫ－８０１在对抗ＤｙｎＡ的损伤中均有一定的疗效。但ＡＰＶ和ＭＫ－８０１本身有一定毒性。而犬尿酸氨是一种内源性物质，主要作用于甘氨酸Ｂ变构调节位点，对整体生理功能影响较小。钙拮抗剂维拉帕米对抗强啡肽的致脊髓损伤作用迅速而完全。在所用剂量（５０ｎｍｏｌ）下无毒副作用。

Dynorphin-induced spinal cord injury in rats

In an attempt to clarify thepathophysiological mechanism of spinal injury and re-covery processes,a dynorphin(ith)spinalneurotoxicity model was established in rats Dyn A(1-17) and its analogues, Dyn A(1-13) and Dyn A(2-17)were all active in the induction of paraplegia,While Dyn A(1-17) was the most potent amongthem This implied that the amino-terminal tyrosineresidue and the car6oxy-terminal amino acid fesiducswere both important for the spinal neurotoxic effectof the native endogenous kappa opiod peptide DynA(1-17) Excitatory amino acid receptor antagonistsDL-2-amino-5-phosphonovaleric acid (APV),kynurenic acid(Kyn) and dizocilpine maleate(MK-801) effectively antagonized dynorphin spinalneurotoxicity. But APV and MK-801 were toxic inthemselves, Kyn as an endogenous allosteric antago-nist of the N-methyl-D-asl)artate receptor is low intoxicity. Its effectiveness in counteracting spinal inju-ry might help incite the development ofa class of effec-tive anti-spinal injury therapeutic agents.A dramaticeffect of calcium antagonist verapamil in resistingdynorphin spinal neurotoxicity was noticed; it wasboth rapid and complete. No toxic or undesirable ef-kcts were noticed in the dose range of 25-50 nmolused in these experiments.