强啡肽对脊髓原生型与诱生型一氧化氮合成酶活性,分布和基因表达的影响

蛛网膜下腔注射强啡肽Ａ１－１７引起剂量依赖性后肢和尾部瘫痪及甩尾甩足抑制。脊髓背角（侧）ＮＭＤＡ受体和ＮＯＳ／ＮＯ功能活性下降可能与Ｄｙｎ镇痛作用有关,脊髓腹角（）ＮＭＤＡ受体－Ｃａ＾２＋－ＮＯＳ／ＮＯ通路过度激活及ｃ－ｆｏｓ高表达可能与Ｄｙｎ致脊髓损伤作用有关。

Effects of dynorphin A1-17 on the activities, immunoreactivities and mRNA expression of cNOS and iNOS in rat spinal cord and their mechanisms

Intrathecal administration(i.t.) of Dynorphin A1-17(Dyn) 1.25-20 nmol produced dose-dependent paralysis of hindlimbs and tail as well as inhibition of tail flick and foot flinch reflexes. The Dyn spinal neurotoxicity and antinociception involve two differential mechanisms: Enhancement of NMDA-Ca(2+)-NOS/NO pathway and c-fos over-expression in the ventral spinal cord for neurotoxicity, and depression of NMDA receptor and NOS activities in the dorsal spinal cord for antinociception. Both brain-derived constitutive NOS (predominant at early stage) and inducible NOS (at later stage) are detrimental, but endothelial constitutive NOS might be beneficial to Dyn spinal neurotoxicity. Dyn exerts a dualistic modulatory effect on Ca2+]i of the cultured rat single spinal neurons, inducing sustained overload of intracellular free calcium via both NMDA and kappa receptor activation at higher concentrations, and producing significant inhibition of the depolarization-evoked calcium influx only via kappa receptor activation at lower concentrations. Dyn exposure for 1 h produced direct neurotoxicity in the cultured spinal neurons within an optimal range of concentrations.