胍丁胺通过抑制大鼠脊髓JNK通路对抗慢性吗啡耐受  

Agmatine blocks chronic morphine antinociceptive tolerance by inhibiting spinal JNK pathway in rats

作　　者：叶裕良 肖亮灿[2] 莫利求[2] 赵春梅[3] 陈培熹[3] 冯鉴强[3] 郭瑞鲜[3] 

机构地区：[1]东莞市横沥医院内科,广东东莞523460 [2]中山大学附属第一医院麻醉科 [3]中山大学中山医学院生理学教研室,广东广州510080

出　　处：《中国药理学通报》2011年第9期1304-1308,共5页Chinese Pharmacological Bulletin

基　　金：广东省科技计划资助项目(No2010B080701035)

摘　　要：目的探讨脊髓c-Jun蛋白氨基末端激酶(c-Jun N-ter-minal kinase,JNK)在胍丁胺抗慢性吗啡镇痛耐受中的作用。方法 SD大鼠皮下注射吗啡(10 mg.kg-1,每日2次,连续9 d)建立慢性吗啡镇痛耐受模型。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(Westernblot)检测脊髓总JNK和磷酸化(p)-JNK蛋白表达;免疫组织化学染色法检测脊髓p-JNK的免疫反应性(immnunoreac-tivity,IR)。结果吗啡耐受大鼠脊髓背角p-JNK-IR明显增多,p-JNK蛋白表达也增多,而总JNK没有改变。胍丁胺(10 mg.kg-1)不仅拮抗吗啡镇痛耐受,而且明显地抑制脊髓背角p-JNK-IR增多及p-JNK蛋白表达上调。结论抑制慢性吗啡注射所引起的脊髓JNK的激活可能是胍丁胺抗吗啡镇痛耐受的作用机制之一。Aim To investigate role of the spinal c-Jun N-terminal kinase （JNK） in attenuation of morphine tolerance to analgesia by agmatine. Methods Mor- phine antinociceptive tolerance was induced by subcu- taneous （s. c. ） injection of twice daily for 9 consecutive Dawley rats. The analgesia morphine （ 10 mg· kg-l ） days in the adult Sprague- effect was assessed by hot- water tail flick test. The expression of total JNK and phosphorylated （p）-JNK were detected by Western blot assay. Immunoreactivity （IR） of p-JNK in the spinal dorsal horn was tested by immunohistochemistry assay. Results The p-JNK-IR and p-JNK protein ex- pression increased in the spinal dorsal horn of chronic morphine antinociceptive tolerance rats. Agmatine （10 mg~ kg-~） not only blocked morphine antinociceptive tolerance, but also significantly attenuated the increa- ses in p-JNK-IR and p-JNK protein expression in the spinal dorsal horn. Conclusion Inhibition of chronic morphine-induced spinal JNK activation may be one of the mechanisms underlying the blockage of morphine antinociceptive tolerance by agmatime.

关 键 词：吗啡 耐受 胍丁胺 JNK 脊髓 镇痛 

分 类 号：R-332[医药卫生] R322.81