脊髓内NMDA受体NR2B在胍丁胺拮抗吗啡耐受中的作用

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(10 mg/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(Western blot)检测脊髓NR2B蛋白表达.结果:皮下注射吗啡的第9 d,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(10 mg/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.

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

Objective: 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.