首页|脊髓Cx43通过JNK通路介导大鼠慢性吗啡镇痛耐受

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

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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10 μl (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-1,10 μl)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 con-nexin 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 μ1 ) 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.

morphine antinociceptive toleranceGap26Cx43JNKc-Junspinal cord

沈宁、郭瑞鲜、胡芬、崔宇、陈培熹、冯鉴强

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中山大学中山医学院生理学教研室,广东,广州,510080

吗啡镇痛耐受 Gap26 Cx43 JNK c-Jun 脊髓

国家自然科学基金广东省自然科学基金广东省医学科学技术研究基金资助项目

81100827S2011040002763A2011153

2013

中国药理学通报
中国药理学会

中国药理学通报

CSTPCDCSCD北大核心
影响因子:1.54
ISSN:1001-1978
年,卷(期):2013.29(3)
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