CCK-8及其受体拮抗剂对吗啡戒断大鼠额叶皮质及海马 CREB 与 pCREB 表达的影响  

Effects of CCK-8 and its receptor antagonists on expression of CREB and pCREB in prefrontal cortex and hippocampus of morphine withdrawal rats

作　　者：高平蕊 马兴友[1] 文迪[1] 杨胜昌[1] 于峰[1] 倪志宇[1] 李淑瑾[1] 马春玲[1] 丛斌[1] 

机构地区：[1]河北医科大学基础医学院法医学系河北省法医学重点实验室,河北石家庄050017

出　　处：《中国病理生理杂志》2014年第7期1158-1165,共8页Chinese Journal of Pathophysiology

基　　金：国家自然科学基金资助项目(No.30672355);河北省自然科学基金资助项目(No.C2007000826)

摘　　要：目的:观察八肽胆囊收缩素(CCK-8)及其受体拮抗剂对吗啡戒断大鼠额叶皮质和海马cAMP反应元件结合蛋白(CREB)表达及其磷酸化(pCREB)的影响,初步探讨CCK-8调节吗啡戒断大鼠的受体后机制。方法:建立大鼠吗啡慢性依赖及纳络酮催促戒断模型,并给予CCK-8、CCK1受体拮抗剂L-364718和CCK2受体拮抗剂LY-288513慢性干预,应用Western blotting和免疫组织化学技术观察额叶皮质和海马CREB与pCREB表达的变化。结果:(1)正常组大鼠额叶皮质神经元胞浆、胞核均表达CREB蛋白,pCREB蛋白则仅在胞核中高表达;海马CA1区锥体细胞层神经元中,CREB蛋白在胞浆中高表达,胞核低表达,pCREB蛋白则仅在胞核中表达。(2)慢性吗啡作用后CREB无明显变化,pCREB增加;急性纳洛酮催促戒断后CREB仍无明显变化,pCREB进一步升高。(3)与戒断组相比,CCK-8、L-364718和LY-288513慢性干预对吗啡依赖戒断大鼠额叶皮质CREB蛋白表达无明显影响,pCREB蛋白表达均明显降低;L-364718和LY-288513慢性干预后,海马CREB与pCREB表达均明显降低,而CCK培慢性干预对CREB蛋白表达无明显影响,仅pCREB蛋白表达明显降低。结论:CCK-8及其受体拮抗剂可能通过调节核转录因子CREB减轻吗啡戒断症状,并具有脑区特异性。AIM：To observe the effects of cholecystokinin octapeptide （CCK-8） and its receptor antagonists on cAMP response element binding protein （ CREB） and phosphorylated CREB （ pCREB） expression in frontal cortex and hippocampus of morphine withdrawal rats , which aim to explore the post-receptor mechanism through which CCK-8 regu-lates morphine withdrawal .METHODS： After the morphine dependence and naloxone-precipitated withdrawal animal models were established, the effects of CCK-8, L-364718 （CCK1 receptor antagonist） and LY-288513 （CCK2 receptor an-tagonist） pretreatment on CREB and pCREB expression in frontal cortex and hippocampus were observed by Western blot -ting and immunohistochemistry .RESULTS：In rat frontal cortex neuron , CREB was expressed in both cytoplasm and nu-cleus, but pCREB was only highly expressed in the nucleus .In the pyramidal cell layer of hippocampal CA 1 region, CREB showed high expression in the cytoplasm and low expression in the nucleus , while pCREB was only expressed in the nu-cleus.No obvious change of CREB was observed after either chronic morphine treatment or naloxone withdrawal .The pCREB expression was increased after chronic morphine treatment and further increased after naloxone withdrawal .Com-pared with the withdrawal group , chronic pretreatment with CCK-8, L-364718 and LY-288513 had no effect on CREB expression in the frontal cortex , but obviously decreased the pCREB expression .In the hippocampus , pretreatment with L-364718 and LY-288513 decreased CREB and pCREB expression , but only the pCREB expression was decreased after CCK-8 treatment.CONCLUSION：CCK-8 and CCK receptor antagonists may alleviate morphine withdrawal symptoms by regulating CREB , with specificity in different brain regions .

关 键 词：吗啡戒断 八肽胆囊收缩素 CAMP反应元件结合蛋白 

分 类 号：R363.14[医药卫生—病理学]