NO对红藻氨酸癫痫发作和IL-6表达的影响  

Expression of IL-6 in kainic acid-induced seizure and regulation roles of nitric oxide pathway

作　　者：孙艺平[1] 孙长凯[1] 范明[2] 赵杰[1] 韩大跃[3] 王吉庆[3] 宫德正[4] 戴淑芳[4] 徐红[4] 

机构地区：[1]大连医科大学脑疾病研究所,大连116027 [2]军事医学科学院基础医学研究所神经生物研究室,北京100850 [3]解放军210医院神经科,大连116021 [4]大连医科大学机能实验室,大连116027

出　　处：《中国药理学通报》2003年第4期397-401,共5页Chinese Pharmacological Bulletin

基　　金：国家自然科学基金资助课题No 3954 0 0 0 2 ;30 0 70 2 6 7

摘　　要：目的　探讨脑内一氧化氮 (NO)介质对癫痫发作及白细胞介素 6(IL 6)表达的影响。方法　采用红藻氨酸 (KA)诱导大鼠癫痫发作 ,以一氧化氮合酶 (NOS)抑制剂L 硝基精氨酸 (L NNA)和NO前体L 精氨酸 (L Arg)进行干预 ,从行为学评估及形态学的角度 ,对KA癫痫发作和IL 6的相关变化做了观察。结果　一次惊厥剂量的KA (1 0mg·kg- 1 )可使动物发生明显的时间相关性癫痫发作 ,并伴随着海马结构、梨状区及大脑皮层等相关脑区IL 6免疫反应(IL 6ir)的快速升高与增强。而经L NNA(50mg·kg- 1 )或与其等摩尔量的L Arg(40mg·kg- 1 )预处理后 ,其癫痫行为发生了明显变化。L NNA促进和加重了癫痫发作 ,KA给药后 3h许多动物死亡 ,而L Arg可使癫痫发作行为减缓。与行为干预相对应 ,L NNA对海马结构等相关脑区内的IL 6ir有明显的上调作用 ,L Arg则显示出相反的效应。结论　内源性NO介质对KA癫痫发作具有抑制作用 ,对IL 6的快速表达具有下调作用 。AIM To explore the role of nitric oxide (NO) mediators in seizure behavior and the related expression of interlukin 6(IL 6). METHODS The IL 6 immunoreactivity (IL 6 ir) and behaviour were observed in kainic acid (KA) induced seizure following pretreatment with L nitroarginine( L NNA), a inhibitor of nitric oxide synthase(NOS), or the same number of moles of L arginine( L Arg). RESULTS The results showed that time dependent seizures were induced on animals after administration of KA (10 mg·kg -1 ), accompanied by the immediate enhancement of IL 6 ir in hippocampal structure, piriform area and cortex. The behaviors of rats were not markedly altered by chronic pretreatment with L NNA (50 mg·kg -1 ) or L Arg (40 mg·kg -1 ). However, after the administration of KA, the seizure behaviors were obviously different in the group of L NNA and L Arg respectively. Seizure was agrevated in the animals with L NNA pretreatment and many rats died at KA 3 hours, whereas seizure was alleviated after KA in the group of L Arg. IL 6 expression was apparently up regulated in some brain areas such as hippocampus in the group of KA pretreated with L NNA, but opposite effects appeared in the group pretreated with L Arg before KA injection. CONCLUSION These results indicate that endogenous NO mediators may alleviate the seizure behaviors and may down regulated the early expression of IL 6 in KA challenged seizure, but it the mechanism of the early expression of IL 6 with the homeostasis of endogenous NO mediator merits further study.nismofthe earlyexpressionofIL 6withthehome

关 键 词：一氧化氮 L-硝基精氨酸 L-精氨酸 红藻氨酸 癫痫 白细胞介素6 

分 类 号：R－332[医药卫生] R322.81