诱导型一氧化氮合酶在强啡肽致脊髓损伤中的作用  

Increases of inducible nitric oxide synthase activity and mRNA expression in rat spinal cord after dynorphin neurotoxicity

作　　者：胡文辉[1] 杨慧芬[1] 强文安 孙秀君[1] 刘娜[1] 万选才[1] 刘景生[1] 任民峰[1] 李芳[2] 王国强[2] 肖剑[2] 廖维宏[2] 

机构地区：[1]中国医学科学院基础医学研究所中国协和医科大学基础医学院 [2]第三军医大学大坪医院野战外科研究所

出　　处：《中国病理生理杂志》1999年第3期217-221,共5页Chinese Journal of Pathophysiology

基　　金：国家自然科学基金

摘　　要：目的：探讨诱导型一氧化氮合酶（ｉＮＯＳ）在强啡肽致脊髓损伤中的作用。方法：［３Ｈ］－左旋精氨酸转化法测定腹侧和背侧脊髓ｉＮＯＳ活性，原位杂交法观测脊髓ｉＮＯＳｍＲＮＡ表达及其细胞分布。结果：大鼠蛛网膜下腔注射（ＩｎＩ）强啡肽Ａ１－１７（Ｄｙｎ）２０ｎｍｏｌ引起持久性截瘫和迟发性神经元死亡；在Ｄｙｎ致瘫后２～３ｈｉＮＯＳｍＲＮＡ表达开始增多增强，４ｈ达高峰，２４ｈ和４８ｈ仍见广泛表达，其分布以胶质细胞和大运动神经元为主；腹侧脊髓ｉＮＯＳ活性在Ｄｙｎ致瘫后４ｈ显著升高，并持续至２４ｈ和４８ｈ；提前１０ｍｉｎＩｎＩ选择性ｉＮＯＳ抑制剂氨基胍１μｍｏｌ可显著对抗Ｄｙｎ２０ｎｍｏｌ引起的持久瘫及伤后４ｈ腹侧脊髓ｉＮＯＳ活性升高。AIM:To explore the role of inducible nitric oxide synthase (iNOS) in dynorphin-induced spinal cord injury. METHODS:The iNOS activities in ventral and dorsal spinal cord were measured with -L-Arginine conversion. The iNOS mRAN expression and its cell distribution were detected with in situ hybridization.RESULTS:Intrathecal injection of dynorphin A 1-17 (Dyn) 20 nmol induced permant paraplegia and delayed neuronal death.The iNOS mRNA expression began to increase at 2～3 h, peaked at 4 h and remained extensive at 24～48 h after Dyn spinal neurotoxicity, predominantly in glia cells and large motoneurons. The iNOS activities in ventral cord significantly increased at 4 h and persisted up to 24～48 h. Intrathecal pretreatment with aminoguanidine 1 μmol, a selective iNOS inhibitor, 10 min before Dyn 20 nmol significantly ameliorated Dyn-induced neurological outcome and antagonized the increase of iNOS activities at 4 h after Dyn neurotoxicity. CONCLUSION:Persistent high expression of iNOS might be involved in the pathophysiology of dynorphin-induced spinal cord injury.

关 键 词：强啡肽 一氧化氮 脊髓损伤 一氧化氮合酶 

分 类 号：R651.202[医药卫生—外科学]