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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。
Objective: To investigate the role of NR2B subunit of N-methyl-D-aspartate (NMDA) receptor in agmatine against morphine tolerance in spinal cord. Methods: A rat model of chronic morphine tolerance was established by subcutaneous injection of morphine (10mg / kg, Bid) into rats. The effect of morphine analgesia was observed by measuring the latency of tail flick with hot water flick method. Spinal cord NR2B protein expression was detected by Western blotting. RESULTS: On the 9th day after morphine injection into the skin, the rats had obvious tolerance to morphine analgesia. At this point, the NMDA receptor NR2B protein expression in the spinal cord of morphine tolerant rats was significantly increased. Agmatine (10 mg / kg) not only antagonized morphine tolerance but also significantly inhibited up-regulation of NR2B protein expression in the spinal cord. Conclusion: Inhibition of chronic morphine injection induces an increase of NR2B subunit of NMDA receptor in spinal cord may be one of the mechanisms of anti-morphine tolerance of agmatine.