脊髓内NMDA受体NR2B在胍丁胺拮抗吗啡耐受中的作用  

Role of the spinal NMDA receptor NR2B subunit in inhibition of morphine tolerance by agmatine

作　　者：李建平 郭瑞鲜[2] 廖新学[3,4] 赵春梅[2] 胡芬[2] 陈培熹[2] 冯鉴强[2] 

机构地区：[1]惠东县人民医院内科,广东惠东516300 [2]中山大学中山医学院生理教研室 [3]中山大学附属第一医院心血管内科 [4]中山大学附属第一医院高血压血管病科,广州510080

出　　处：《中国临床解剖学杂志》2009年第4期452-454,共3页Chinese Journal of Clinical Anatomy

基　　金：广东省科技计划项目(2008B080703053)

摘　　要：目的:探讨脊髓N-甲基-D-天门冬氨酸(N-methyl-D-aspartate,NMDA)受体NR2B亚单位在胍丁胺抗吗啡耐受中的作用。方法:给大鼠皮下注射吗啡(10mg/kg,Bid)建立慢性吗啡耐受大鼠模型。应用热水甩尾法测定甩尾潜伏期观察吗啡的镇痛效果。应用免疫印迹法(Westernblo)t检测脊髓NR2B蛋白表达。结果:皮下注射吗啡的第9d,大鼠对吗啡镇痛已产生明显的耐受。此时,吗啡耐受大鼠脊髓NMDA受体NR2B蛋白表达显著增多。胍丁胺(10mg/kg)不仅拮抗吗啡耐受,而且明显地抑制脊髓NR2B蛋白表达上调。结论:抑制慢性吗啡注射引起脊髓NMDA受体NR2B亚单位增多可能是胍丁胺抗吗啡耐受的作用机制之一。Objectivo： To investigate the role of the spinal N-methyl-D-aspartate （NMDA） receptors NR2Bsubunit in attenuation of morphine tolerance by agmatine. Methods： Adult Sprague-dawley rats were injected morphine （10 mg/kg） subcutaneously twice daily to set up the chronic morphine tolerance model. The analgesia effect was assessed by hot-water tail flick test. The expression of NMDA receptor NR2B subunit was detected by western blot assay. Results： Morphine injection for 9 days markedly induced morphine antinociceptive tolerance, accompanied by the increase of NR2B protein expression. Agmatine （10 mg/kg） not only blocked morphine tolerance, but also significantly attenuated the increases in spinal NR2B protein expression. Conclusions： Inhibition of chronic morphine-induced increased NMDA receptor NR2B subunit may be one of the mechanisms underlying the blocking of morphine tolerance by agmatine.

关 键 词：NR2B亚单位 NMDA受体 吗啡耐受 脊髓内 胍丁胺 拮抗 D-天门冬氨酸 大鼠模型 

分 类 号：R392-33[医药卫生—免疫学] R338[医药卫生—基础医学]