L-NAME加重强啡肽致脊髓损伤作用  

L- NAME AGGRAVATES DYNORPHIN-INDUCED SPINAL CORD INJURY IN RATS

作　　者：胡文辉[1] 刘娜[2,3] 孙秀君[2,3] 任军 杨慧芬 任民峰[2,3] 

机构地区：[1]第三军医大学野战外科研究所,重庆430042 [2]中国医学科学院基础医学研究所 [3]中国协和医科大学基础医学院,北京100005

出　　处：《神经科学》1997年第3期115-119,124,共6页Chinese Journal of Neuroscience

基　　金：国家自然科学基金!39370786

摘　　要：大鼠脊髓蛛网膜下腔注射（i．t．）强啡肽A(1-17)（DynorphinA(1-17)，Dyn）1．25～20nmol可引起剂量依赖性后肢和尾部瘫痪。其中1．25和2．5nmol对运动功能无影响；10nmol为致一过性瘫痪剂量，脊髓无明显病理变化；20nmol为致持久性瘫痪剂量，脊髓发生进行性中央性坏死。一氧化氮合成酶抑制剂N-硝基-左旋精氨酸甲酯（L－NAME）i．t．1～5μmol时对正常大鼠后肢功能无影响，但在i．t．10和20μmol时可引起一过性瘫痪。提前10mini．t．L－NAME1μmol并不能对抗i．t．Dyn20nmol的致持久瘫痪和不可逆性脊髓损伤作用．反而使i．Dyn10nmol引起的一过性瘫痪转为持久瘫痪，即加重其致瘫作用。L－NAME1μmol与低剂量Dyn1．25nmol和2．5nmol合用后，分别导致7／12和5/7只大鼠出现一过性瘫痪。结果表明L-NAME不能对抗反而加重Dyn致脊髓损伤作用。Intrathecal injection(i. t. ) of Dynorphin A1 - 17 (DYn) 1. 25 -20 nmol produced dose-depen-dent paralysis of hindlimbs and tail in rats. Dyn 1. 25 nmol and 2. 5 nmol did not affect motor function. Dyn 10nmol induced only transient paralpsis with no obvious pathological (by Nissl stain), but Dyn 20 nmolproduced permanent paraplegia with irreversible spinal cord damage, characterizde by central and progressivenecrosis. In normal rats, i. t. 1~5μmol of N00- Nitro- L - Arginine Methyl Ester (L- NAME), an inhibitor toconstitutive nitric oxide synthase, had no effect on hindlimb motor functioon but i. t. 10 and 20 μmolinduced transientand delayed paralysis. Pretreatment with L - NAME 1 μmol did not antagonize Dyn 20 nmol- induced permanentparaplegia but aggravated for 10 nmol - induced paralysis into permanent paraplegia.Pretreatment withL- NAME 1 μmol 10 min before i. t. low dose of Dyn 1.25 and 2.5 nmol induced transient paralysis in 7 out of12 and 5 out of 6 rats respectively.These results suggested that L - NAME not antagonize but worsened Dyn- induced spinal cord injury.

关 键 词：强啡肽 一氧化氮合成酶 脊髓损伤 

分 类 号：R651.202[医药卫生—外科学]