CAJ | 학술논문

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-8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。
목적：관찰팔태담낭수축소（CCK-8）급기수체길항제대마배계단대서액협피질화해마cAMP반응원건결합단백（CREB）표체급기린산화（pCREB）적영향，초보탐토CCK-8조절마배계단대서적수체후궤제。방법：건립대서마배만성의뢰급납락동최촉계단모형，병급여CCK-8、CCK1수체길항제L-364718화CCK2수체길항제LY-288513만성간예，응용Western blotting화면역조직화학기술관찰액협피질화해마CREB여pCREB 표체적변화。결과：（1）정상조대서액협피질신경원포장、포핵균표체CREB단백，pCREB단백칙부재포핵중고표체；해마CA1구추체세포층신경원중，CREB단백재포장중고표체，포핵저표체，pCREB단백칙부재포핵중표체。（2）만성마배작용후CREB무명현변화， pCREB증가；급성납락동최촉계단후CREB잉무명현변화， pCREB진일보승고。（3）여계단조상비，CCK-8、L-364718화LY-288513만성간예대마배의뢰계단대서액협피질CREB단백표체무명현영향，pCREB단백표체균명현강저；L-364718화LY-288513만성간예후，해마CREB여pCREB표체균명현강저，이CCK-8만성간예대CREB단백표체무명현영향，부pCREB단백표체명현강저。결론：CCK-8급기수체길항제가능통과조절핵전록인자CREB감경마배계단증상，병구유뇌구특이성。
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 .