鞘内注射U0126对吗啡戒断大鼠脊髓神经元磷酸化CREB表达的影响  

EFFECTS OF INTRATHECAL INJECTION OF U0126 ON THE EXPRESSION OF PHOSPHO-CREB IN SPINAL CORD OF MORPHINE-INDUCED WITHDRAWAL RATS

作　　者：刘海林[1] 曹君利 戴培静[1] 郑国龙[1] 曾因明 

机构地区：[1]南京医科大学附属淮安市第一人民医院麻醉科,江苏淮安223300 [2]江苏省麻醉医学重点实验室,江苏徐州221002

出　　处：《中国应用生理学杂志》2007年第1期5-8,I0005,共5页Chinese Journal of Applied Physiology

基　　金：国家自然科学基金资助项目(30200267);江苏省教委自然科学基金资助课题(01KJD320036);江苏省淮安市科技发展计划(HAS05029)

摘　　要：目的:研究鞘内注射细胞外信号调节激酶(ERK)抑制剂U0126对吗啡依赖大鼠纳洛酮催促戒断反应、脊髓磷酸化cAMP反应元件结合蛋白(p-CREB)表达的影响。方法:建立大鼠吗啡依赖和戒断模型,分为正常对照组、吗啡依赖组、吗啡戒断组、U0126组、溶媒(DMSO)组,采用行为学(n=8)、免疫组织化学(n=6)和Western blot(n=4)方法观察鞘内应用U0126对吗啡依赖大鼠纳洛酮催促戒断反应、脊髓p-CREB表达的影响。结果:①鞘内注射U0126可明显减轻吗啡依赖大鼠戒断症状,戒断组戒断症状评分为28.6±4.89,U0126组为22.5±4.09(P<0.05);戒断组促诱发痛评分(TEA score)为13.5±2.55,U0126组为10.0±2.76(P<0.05)。②鞘内注射U0126可明显减少胸腰段脊髓背角p-CREB阳性神经元的数目,U0126组为287±54,低于戒断组(380±71,P<0.05)。③western blot结果显示:鞘内注射U0126明显抑制吗啡戒断期间脊髓p-CREB表达的增加。结论:鞘内注射U0126能明显抑制吗啡戒断大鼠脊髓神经元p-CREB的表达。Aim： To explore effects of intrathecal injection of U0126 on morphine withdrawal response and the spinal Phospho-CREB expression in morphine-induced withdrawal rats. Methods： All the rats were divided into 5 groups： control group, dependence group, withdrawal group, U0126 group（5μg, it）and DMSO group. Morphine withdrawal .score, touch evoked agitation scores（TEA score）, immunohistochemical and Western-blotting technique were used to evaluate morphine withdrawal response and the expression of Phos- pho-CREB in the spinal cord. Results： Intrathecal injection of MEK inhibitor U0126 significantly alleviated morphine withdrawal symptoms. Morphine withdrawal scores in U0126 group（22.5± 4.09） were significantly lower than that of withdrawal group（28.6 ±4.89,P〈0.05）. TEA score of withdrawal group was 13.5 ± 2.55, which was significantly higher than that of U0126 group （10.0± 2.76,P〈0.05）. Phospho-CREB positive neurons in the spinal dorsal horn of withdrawal group were 380± 71, which is higher than that of U0126 group（293± 47, P〈 0.05）. Compared with withdrawal group, level of Phospho-CREB protein detected by Western blot in spinal cord of U0126 group was significantly lower. Conclusion： MEK inhibitors U0126 could suppress expression of Phospho-CREB in the spinal cord.

关 键 词：吗啡 戒断 脊髓 细胞外信号调节激酶 CAMP反应元件结合蛋白 

分 类 号：R322.8[医药卫生—人体解剖和组织胚胎学]