神经元性一氧化氮合酶在强啡肽致瘫和镇痛中的作用

目的 探讨神经元性原生型一氧化氮合酶（ｎｃＮＯＳ）在强啡肽（Ｄｙｎ）Ａ（１－７）致瘫和镇痛中的不同作用。方法 采用ｎｃＮＯＳ免疫组织化学和＾３Ｈ－左旋精氨酸转化技术,观测Ｄｙｎ致瘫和镇痛过程中ｎｃＮｏＳ活性和免疫活性（ＩＲ）变化,并探讨ｎｃＮＯＳ选择性抑制剂７－硝基吲唑对Ｄｙｎ致瘫和镇痛作用的影响。结果 ＤｙｎＡ（１－１７）蛛网膜下腔注射引起的剂量相关性后肢和尾部瘫痪及甩尾甩足抑制;ＤｙｎＡ（１－

Role of neuronal nitric oxide synthase in dynorphin spinal neurotoxicity and analgesia in rats

OBJECTIVE: To investigate the different role of neuronal constitutive nitric oxide synthase (nc-NOS) in dynorphin (Dyn) A(1-17) spinal neurotoxicity and analgesia. METHODS: The cNOS activity in ventral and dorsal spinal cord in rats was measured with H-L-arginine conversion, and ncNOS immunoreactivity(IR) was observed with strepavidin-peroxidase immunohisto-chemistry. RESULTS: Intrathecal administration of Dyn A(1-17) produced dose-dependent paralysis of hindlimbs and tail as well as inhibition of tail flick (TF) and foot flinch (FF) reflexes. Dyn A(1-17) 10 nmol induced only transient paralysis and apparently reduced the ncNOS-IR in the superficial dorsal horn but did not induce any change of ncNOS-IR in the ventral horn cells as compared with saline control. Dyn A(1-17) 20 nmol produced permanent paraplegia with irreversible spinal cord damage, characterized by central and progressive necrosis. Dyn A(1-17) 20 nmol remarkedly induced the expression of ncNOS-IR in the ventral horn cells whereas inhibited ncNOS-IR in the superficial dorsal horn. Dyn A(1-17) 20 nmol also significantly increased the activities of cNOS in the ventral spinal cord but did not affect cNOS activities in the dorsal spinal cord. Intrathecal pretreatment with 7-nitroindazole (7-NI) 1 mumol, a selective ncNOS inhibitor 10 min prior to i.t. Dyn A(1-17) 20 nmol significantly ameliorated Dyn-induced neurological outcome, but TF and FF remained inhibited. 7-nitroindazole also significantly antagonized the increases of cNOS activities and ncNOS-IR in the ventral spinal cord at 4 h after i.t. Dyn A(1-17) 20 nmol, but did not affect or even potentiated Dyn-induced inhibition of cNOS activity and ncNOS-IR in the dorsal spinal cord. CONCLUSIONS: Over-expression or over-activation of ncNOS in the ventral spinal cord may be involved in Dyn spinal neurotoxicity, whereas as the reduction of ncNOS activities in the dorsal spinal cord might reflect Dyn spinal analgeisia or pain modulation.