急性或慢性吗啡依赖和戒断对大鼠脑组织CREB-1表达的影响  

Effects of acute and chronic morphine dependence and withdrawal on CREB-1 protein expression in rat brain

作　　者：傅强[1] 王新华[2] 傅骁勇[3] 张宏[1] 米卫东[1] 

机构地区：[1]解放军总医院麻醉手术中心,北京市100853 [2]同济大学附属东方医院麻醉科 [3]第二军医大学附属东方肝胆外科医院信号转导研究中心

出　　处：《中华麻醉学杂志》2006年第7期628-630,共3页Chinese Journal of Anesthesiology

基　　金：国家自然科学基金资助项目(39870757)

摘　　要：目的研究急性或慢性吗啡依赖和戒断大鼠脑组织环腺苷酸反应元件结合蛋白-1 (CREB-1)表达的变化。方法雄性SD大鼠30只,随机分为5组(n=6):空白对照组、急性吗啡依赖组、急性吗啡戒断组、慢性吗啡依赖组、慢性吗啡戒断组。急性吗啡依赖组每次背部皮下注射吗啡5 mg/kg,间隔2 h,连续8次;急性吗啡戒断组在急性吗啡依赖后3 h腹腔注射纳洛酮5 mg／kg,催促戒断30 min后处死大鼠。慢性吗啡依赖组每日吗啡用量分3次腹腔注射,从第一天用量5 mg/kg起,直到第12天递增至260 mg／kg,慢性吗啡戒断组在慢性吗啡依赖后的次日腹腔注射纳洛酮5 mg/kg,催促戒断24h后处死大鼠。用Western-blot法测定大脑皮层、伏隔核及海马CREB-1表达。结果与空白对照组比较,急性吗啡依赖、戒断组皮层、伏隔核和海马CREB-1表达差异无统计学意义(P>0．05),慢性吗啡依赖、戒断组皮层、海马CREB-1表达上调,伏隔核CREB-1表达下调(P<0．05);与慢性吗啡依赖组比较,慢性吗啡戒断组伏隔核CREB-1表达下调(P<0．05)。结论急性吗啡依赖、戒断对脑组织CREB-1表达无影响;而慢性吗啡依赖、戒断后不同脑区CREB-1表达不同。Objective To investigate the changes in CREB-1 protein expression in three brain regions induced by acute or chronic morphine dependence and withdrawal. Methods Thirty SD rats of both sexes weighing 180-220 g were randomly divided into 5 groups （ n = 6 each） ; group Ⅰ acute morphine dependence; group Ⅱ acute morphine abstinence; group Ⅲ chronic morphine dependence; group Ⅳ chronic morphine abstinence and group Ⅴ control. Acute morphine dependence was induced by subcutaneous injection of morphine 5 mg · kg^- 1 every 2h × 8. Acute morphine abstinence was induced by intraperitoneal （IP） naloxone 5 mg·kg^-1 3 h after last dose of morphine. The animals were killed 30 min later. Chronic morphine dependence was induced by increasing doses of morphine, starting form 5 mg·kg^-1·day^-1 to 260 mg·kg^-1·day^-1 in 12 days. The daily dose was given by 3 subcutaneous injections. Chronic morphine abstinence was induced by IP naloxone 5 mg·kg^-1. The animals were killed 24 h later. The brains were removed and the cortex, nucleus accumbens and hippocampus were separated. The relative expression of CREB-1 protein was determined by Western-blot. Results The CREB-1 protein expressions in cortex, nucleus accumbens and hippocampus in acute morphine dependence and abstinence groups （group Ⅰ and Ⅱ ） was not significantly different from that in control group （ P 〉 0.05）. The CREB-1 protein expression in cortex and hippocampus was significantly up-regulated while that in nucleus accumbens was significantly down-regulated in chronic morphine dependence and abstinence group （ group Ⅲ and Ⅳ ） as compared with control group. The CREB-1 protein expression in nucleus accumbens in group Ⅳ was significantly lower than that in group Ⅲ . Conclusion Acute morphine dependence and abstinence do not significantly affect CREB-1 protein expression in the brain. The changes in CREB-1 protein expression are different in different brain regions in chronic morphine dependence and abstinence rats.

关 键 词：吗啡依赖 物质戒断综合征 DNA结合蛋白质 环AMP反应性 脑 

分 类 号：R749.64[医药卫生—神经病学与精神病学]