本文選題：嗎啡戒斷 + 八肽膽囊收縮素��； 參考：《中國病理生理雜志》2014年07期

【摘要】：目的:觀察八肽膽囊收縮素(CCK-8)及其受體拮抗劑對嗎啡戒斷大鼠額葉皮質(zhì)和海馬cAMP反應(yīng)元件結(jié)合蛋白(CREB)表達及其磷酸化(pCREB)的影響,初步探討CCK-8調(diào)節(jié)嗎啡戒斷大鼠的受體后機制。方法:建立大鼠嗎啡慢性依賴及納絡(luò)酮催促戒斷模型,并給予CCK-8、CCK1受體拮抗劑L-364718和CCK2受體拮抗劑LY-288513慢性干預(yù),應(yīng)用Western blotting和免疫組織化學(xué)技術(shù)觀察額葉皮質(zhì)和海馬CREB與pCREB表達的變化。結(jié)果:(1)正常組大鼠額葉皮質(zhì)神經(jīng)元胞漿、胞核均表達CREB蛋白,pCREB蛋白則僅在胞核中高表達;海馬CA1區(qū)錐體細胞層神經(jīng)元中,CREB蛋白在胞漿中高表達,胞核低表達,pCREB蛋白則僅在胞核中表達。(2)慢性嗎啡作用后CREB無明顯變化,pCREB增加;急性納洛酮催促戒斷后CREB仍無明顯變化,pCREB進一步升高。(3)與戒斷組相比,CCK-8、L-364718和LY-288513慢性干預(yù)對嗎啡依賴戒斷大鼠額葉皮質(zhì)CREB蛋白表達無明顯影響,pCREB蛋白表達均明顯降低;L-364718和LY-288513慢性干預(yù)后,海馬CREB與pCREB表達均明顯降低,而CCK培慢性干預(yù)對CREB蛋白表達無明顯影響,僅pCREB蛋白表達明顯降低。結(jié)論:CCK-8及其受體拮抗劑可能通過調(diào)節(jié)核轉(zhuǎn)錄因子CREB減輕嗎啡戒斷癥狀,并具有腦區(qū)特異性。
[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.
【作者單位】： 河北醫(yī)科大學(xué)基礎(chǔ)醫(yī)學(xué)院法醫(yī)學(xué)系河北省法醫(yī)學(xué)重點實驗室;
【基金】：國家自然科學(xué)基金資助項目(No.30672355) 河北省自然科學(xué)基金資助項目(No.C2007000826)
【分類號】：R363.14

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