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~

发布时间：2018-05-12 15:18

本文选题：吗啡戒断 + 八肽胆囊收缩素　；参考：《中国病理生理杂志》2014年07期

【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。
[Abstract]:Aim: to observe the effects of cholecystokinin octapeptide (CCK-8) and its receptor antagonist on the expression and phosphorylation of cAMP response element binding protein (cAMP) in frontal cortex and hippocampus of morphine abstinent rats, and to explore the mechanism of CCK-8 regulating the receptor in morphine withdrawal rats. Methods: chronic morphine dependence and naloxone-precipitated withdrawal model were established in rats. CCK-8 CCK1 receptor antagonist L-364718 and CCK2 receptor antagonist LY-288513 were given chronic intervention. The expression of CREB and pCREB in frontal cortex and hippocampus were observed by Western blotting and immunohistochemistry. Results (1) in normal group, the expression of CREB protein in the cytoplasm of frontal cortex neurons was only high in the nucleus, and in the pyramidal layer neurons of the hippocampal CA1 area, the expression of the protein was high in the cytoplasm. The low expression of pCREB protein was only found in the nucleus. (2) there was no significant change in CREB after chronic morphine treatment, and the expression of pCREB was increased. Compared with abstinence group, CCK-8 L-364718 and LY-288513 chronic intervention had no significant effect on the expression of CREB protein in frontal cortex of morphine dependent rats. After chronic intervention with L-364718 and LY-288513, The expression of CREB and pCREB in hippocampus was significantly decreased, while the expression of CREB protein was not affected by chronic CCK culture, only the expression of pCREB protein was significantly decreased. Conclusion the effects of the receptor antagonist of 1: CCK-8 and its receptor antagonist on morphine withdrawal may be alleviated by regulating nuclear transcription factor CREB, and may be specific to the brain region.
【作者单位】：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;
【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)
【分类号】：R363.14

【相似文献】