鞘内注射右美托咪定对吗啡戒断大鼠脊髓磷酸化环磷酸腺苷反应元件结合蛋白表达的影响  

Effects of intrathecal injection of dexmedetomidine on p-CREB expression in spinal cord in naloxoneinduced withdrawal response of morphine-dependent rats

作　　者：郑国龙[1] 刘海林[1] 

机构地区：[1]南京医科大学附属淮安第一医院麻醉科,江苏省223300

出　　处：《江苏医药》2014年第22期2673-2676,F0002,共5页Jiangsu Medical Journal

基　　金：南京医科大学科技发展基金重点项目(2012NJMU152)

摘　　要：目的探讨鞘内注射右美托咪定对吗啡戒断大鼠脊髓磷酸化环磷酸腺苷反应元件结合蛋白(p-CREB)表达的影响。方法 40只雄性成年SD大鼠随机均分为吗啡依赖组(MD组)、吗啡戒断组(MW组)、右美托咪定组(DEX组)和对照组(C组)。MD、MW、DEX组建立吗啡依赖模型。MW组和DEX组腹腔注射纳洛酮4mg/kg激发吗啡戒断反应。注射纳洛酮前30min,DEX组鞘内注射右美托咪定3μg/kg。注射纳洛酮后1h内观察大鼠戒断反应和痛觉异常反应。处死大鼠,取脊髓组织,采用免疫组化法和Western blot法检测p-CREB的表达。结果与MW组比较,DEX组戒断症状评分和促诱发痛评分均降低(P<0.05);与C组比较,MW组大鼠脊髓背角p-CREB表达上调(P<0.05);与MW组比较,DEX组大鼠脊髓p-CREB表达下调(P<0.05)。结论鞘内注射右美托咪定可能通过抑制脊髓p-CREB的表达而减轻吗啡依赖大鼠戒断反应。Objective To explore the effects of intrathecal injection of dexmedetomidine on the expression of phosphorylation of cyclic AMP response element-binding protein（p-CREB） in the spinal cord in naloxone-induced withdrawal response of morphine-dependent rats. Methods Forty male adult SD rats were equally and randomly divided into 4 groups of MD, MW, DEX and C（normal controls）. The morphine-dependent rat models were established in groups of MD, MW and DEX. Morphine withdrawal response was induced by intraperitoneal injection of naloxone 4 mg/kg in groups of MW and DEX. Dexmedetomidine 3 μg/kg was intrathecally injected at 30 minutes before naloxone administration in group DEX. Morphine withdrawal response and touch-evoked agitation were observed during 1 hour after naloxone administration. The animals were then sacrificed and the spinal cords were removed for detecting the expression of p-CREB by immunohischemistry and Western blot. Results Compared with group MW, morphine withdrawal response score and touch-evoked agitation score were decreased in group DEX（P〈0. 05）. Compared with group C, p-CREB expression in the spinal cord was upregulated in group MW（P〈0. 05）. Compared with group MW, p-CREB expression in the spinal cord was downregulated in group DEX（P〈0.05）. Conclusion Intrathecal injection of dexmedetomidine can alleviate morphine withdrawal response through inhibiting the p-CREB expression in rat spinal cord.

关 键 词：右美托咪定 戒断反应 环磷酸腺苷反应元件结合蛋白 

分 类 号：R971[医药卫生—药品]