脊髓Cx43通过JNK通路介导大鼠慢性吗啡镇痛耐受  

Spinal Cx43 mediates chronic morphine antinociceptive tolerance through JNK pathway in rats

作　　者：沈宁[1] 郭瑞鲜[1] 胡芬[1] 崔宇[1] 陈培熹[1] 冯鉴强[1] 

机构地区：[1]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》2013年第3期372-376,共5页Chinese Pharmacological Bulletin

基　　金：国家自然科学基金资助项目(No 81100827);广东省自然科学基金资助项目(No S2011040002763);广东省医学科学技术研究基金资助项目(No A2011153)

摘　　要：目的探讨脊髓缝隙连接蛋白43(connexin 43,Cx43)在慢性吗啡镇痛耐受中的作用及其是否通过JNK通路介导慢性吗啡镇痛耐受。方法 Sprague-Dawley(SD)成年♂大鼠连续7 d鞘内注射吗啡10μl(1.5 g.L-1)建立慢性吗啡镇痛耐受模型。采用热辐射甩尾法测定甩尾潜伏期以观察吗啡的镇痛效果。应用Western blot法检测Cx43、磷酸化JNK(p-JNK)、总JNK(t-JNK)、磷酸化c-Jun(p-c-Jun)和总c-Jun(t-c-Jun)的表达;免疫组织荧光染色法检测脊髓Cx43的免疫反应性(immnunoreactivity,IR)。结果吗啡耐受引起大鼠脊髓Cx43的表达明显增多;Gap26(特异性Cx43阻断剂,1.5 g.L-1,10μl)可以拮抗吗啡镇痛耐受,并且明显地抑制慢性吗啡镇痛耐受所致的脊髓JNK及c-Jun的激活。结论脊髓Cx43通过JNK通路介导大鼠慢性吗啡镇痛耐受。Aim To investigate the role of spinal connexin 43（Cx43） in the development of chronic morphine antinociceptive tolerance and whether the c-Jun N-terminal kinase（JNK） pathway was involved in this role.Methods Morphine 10 μl（1.5 g · L-1） was adminitered intrathecally for consecutive 7 days to establish the model of chronic analgesic tolerance to morphine in the adult ♂ Sprague-Dawley rats.Hot radiation tail flick test was used to assess the analgesic efficacy.Western blot assay was applied to detect the expressions of Cx43,phosphorylated（p）-JNK,total（t）-JNK,p-c-Jun and t-c-Jun.Results On the 7th day of repeated intrathecal injection of morphine,the expression of Cx43 was remarkably increased in the lumbar spinal cord.Coadministration of Gap26（a specific inhibitor of Cx43,1.5 g · L-1,10 μl） with morphine obviously attenuated not only morphine antinociceptive tolerance,but also the activiation of the JNK and c-Jun induced by chronic morphine treatment.Conclusion The spinal Cx43 mediates morphine antinociceptive tolerance through JNK pathway in rats.

关 键 词：吗啡镇痛耐受 Gap26 CX43 JNK C-JUN 脊髓 

分 类 号：R-332[医药卫生] R322.81