摘要
目的:应用清醒大鼠脑微透析技术以选择性可溶性鸟苷酸环化酶抑制剂1H-犤1,2,4犦恶二唑犤4,3-A犦喹喔啉-1-酮为工具药观察大鼠纹状体一氧化氮-环鸟苷酸信号转导。方法:实验于2004-02/08在锦州医学院药理教研室完成,选择雄性健康SD大鼠35只,平衡麻醉液麻醉后,将大鼠固定在立体定位仪上,横跨纹状体植入一透析探头,待大鼠清醒后24h进行透析灌流实验,灌流速度为5mL/min,每20min收集1次透析液,用放射免疫方法测定环鸟苷酸含量。结果:35只大鼠均进入结果分析。①纹状体内局部灌流1H-犤1,2,4犦恶二唑犤4,3-A犦喹喔啉-1-酮10,50,100μmol/L可剂量依赖性降低细胞外基础环鸟苷酸水平,1H-犤1,2,4犦恶二唑犤4,3-A犦喹喔啉-1-酮100μmol/L作用最强,最大,可使细胞外基础环鸟苷酸水平降低约50%。②1H-犤1,2,4犦恶二唑犤4,3-A犦喹喔啉-1-酮100μmol/L可完全对抗N-甲基-D-天冬氨酸(250μmol/L)引起的细胞外环鸟苷酸水平增加。③1H-犤1,2,4犦恶二唑犤4,3-A犦喹喔啉-1-酮也可阻断一氧化氮供体S-亚硝基-N-乙酰青霉胺(1mmol/L)引起的细胞外环鸟苷酸水平增加。纹状体内局部灌流a-氨基羟甲基异恶唑丙酸(100μmol/L)不能使环鸟苷酸水平增加。结论:①在基础状态下纹状体的环鸟苷酸约50%来源于可溶性鸟苷酸环化酶的激活。②纹状体的一氧化氮-环鸟苷酸神经通路的激活是通过N-甲基-D-天冬氨酸受体完成的。③在大鼠纹状体一氧化氮也是通过激活可溶性鸟苷酸环化酶而使环鸟苷酸增加的。
AIM：The nitric oxide-cyclic GMP signalling transduction was studied with a selective inhibitor of soluble guanylyl cyclasc, 1 H（1,2,4）oxadiazolo[4,3-a] quiNOxalin-l-one （ODQ）, during microdialysis of the rat striatum. METHODS： Male Sprague-Dawley rats were anesthetized with equithesin. A microdialysis probe was transversely implanted in the striatum. After a 24 hours recovery period, the microdialysis probes were perfused at 5 mL×min^-1. Samples were collected every 20 minutes following a washout period of 1 hour. CGMP was determined by radioimmunoassay method. RESULTS： Intrastriatal infusion of ODQ 10, 50, 100 μmol×L^-1 inhibited, in a concentration-dependent manner, the basal extracellular level of cGMP. The maximal inhibition amounted to about 50 %, ODQ 100 mmol×L^-1 completely inhibited the cGMP elevation evoked by N-methyl-D-aspartare （NMDA, 250μmol×L^-1）. ODQ also prevented cGMP elevation in response to the NO generator S-nitroso-N-acetylpenicillamine （SNAP, 1mmol×L^-1）. The administration of a-amiNO-3-hydroxy-5-methyl-4-isoxazolepropionic acid （AMPA, 100μmol×L^-1） in the striatum did not significantly increase extracellular cGMP. CONCLUSION：①The results suggest that under basal condition, about 50 % of the cGMP in the striatum seem to originate from the soluble guanylyl cyclase. ②Under basal condition, glutamatergic striatal inputs could stimulate a NO-cGMP pathway in the striatum via NMDA receptors.③It was proved further that NO elicits cGMP accumulation in target cells by stimulating soluble guuanylyl cyclase in the striatum.
出处
《中国临床康复》
CSCD
北大核心
2005年第32期132-134,共3页
Chinese Journal of Clinical Rehabilitation
基金
辽宁省教育委员会基金资助课题(202173362)~~
