本文選題：咯利普蘭 + 抑郁�。� 參考：《中國(guó)病理生理雜志》2017年02期

【摘要】：目的:研究磷酸二酯酶4(PDE4)抑制劑咯利普蘭對(duì)酒精中毒戒斷誘導(dǎo)的抑郁樣行為的作用及對(duì)小鼠海馬和前額葉皮質(zhì)腦區(qū)環(huán)磷酸腺苷(cAMP)、蛋白激酶A(PKA)、cAMP反應(yīng)元件結(jié)合蛋白(CREB)、磷酸化CREB(p-CREB)和腦源性神經(jīng)營(yíng)養(yǎng)因子(BDNF)表達(dá)的影響。方法:取60只雄性ICR小鼠,隨機(jī)分為空白對(duì)照組、空白+咯利普蘭組、慢性酒精模型組和咯利普蘭治療組(0.1、0.5和1 mg/kg)。給予酒精28 d期間每周進(jìn)行酒精戒斷處理。慢性酒精處理后,進(jìn)行強(qiáng)迫游泳測(cè)試(FST)和懸尾測(cè)試(TST),觀察小鼠抑郁樣行為;ELISA檢測(cè)小鼠海馬和前額葉皮質(zhì)cAMP含量,Western blot檢測(cè)小鼠海馬和額葉皮質(zhì)PKA、CREB、p-CREB和BDNF的表達(dá)。結(jié)果:隨著飲酒天數(shù)及戒斷次數(shù)的增加,小鼠表現(xiàn)出明顯嗜酒現(xiàn)象,飲酒量增加(P0.01),FST和TST測(cè)試中的不動(dòng)時(shí)間增加(P0.01)。小鼠給藥咯利普蘭(0.5和1 mg/kg)28 d后,FST和TST不動(dòng)時(shí)間與模型組相比明顯減少(P0.05),且能改善小鼠的嗜酒現(xiàn)象,小鼠飲酒量與模型組相比明顯減少(P0.01);相比于正常組,模型組小鼠海馬和前額葉皮質(zhì)cAMP含量明顯降低(P0.01),并且海馬和額葉皮質(zhì)PKA、p-CREB和BDNF也明顯低于正常水平(P0.01)�？├仗m(0.5和1 mg/kg)給藥28 d后,海馬與前額葉皮質(zhì)cAMP含量明顯增加(P0.01),酒精抑制的海馬腦區(qū)PKA、p-CREB和BDNF表達(dá)被逆轉(zhuǎn)(P0.05),且酒精抑制的前額葉皮質(zhì)PKA和p-CREB表達(dá)被逆轉(zhuǎn)(P0.05)。結(jié)論:磷酸二酯酶4抑制劑咯利普蘭能明顯改善酒精中毒及戒斷引起的抑郁樣癥狀,且能減輕嗜酒癥狀,機(jī)制可能涉及第二信使cAMP通路�？├仗m通過(guò)抑制PDE4,增加海馬與前額葉皮質(zhì)cAMP水平,進(jìn)而激活PKA-CREB-BDNF通路,從而產(chǎn)生抗抑郁作用。
[Abstract]:Aim: to study the effects of phosphodiesterase 4 (PDE4) inhibitor Rolipram on depressive behavior induced by abstinence from alcoholism and its effects on camp, protein kinase A (PKA) and camp response element binding protein (CREB) in hippocampus and prefrontal cortex of mice. Effects of phosphorylated CREB (p-CREB) and brain-derived neurotrophic factor (BDNF). Methods: sixty male ICR mice were randomly divided into three groups: blank control group, chronic alcohol model group and clolipram treatment group (0.1 and 1 mg/kg). Alcohol withdrawal was given weekly for 28 days. After chronic alcohol treatment, forced swimming test (FST) and tail suspension test (TST) were used to detect camp content in hippocampus and prefrontal cortex of mice by Elisa. Results: with the increase of drinking days and abstinence times, mice showed obvious alcoholism, and the immobility time in FST and TST test increased (P0.01). The immobility time of FST and TST in mice was significantly decreased compared with the model group (P0.05) after administration of Rolipram (0. 5 and 1 mg/kg) for 28 days (P0.05), and the alcohol consumption in mice was significantly decreased compared with that in the model group (P0. 01), and compared with that in the normal group (P0. 01). The camp contents in hippocampus and prefrontal cortex were significantly decreased in model group (P0.01), and PKAP-CREB and BDNF in hippocampus and frontal cortex were also significantly lower than those in normal group (P0.01). The camp content in hippocampus and prefrontal cortex was significantly increased (P0.01), the expression of PKAP-CREB and BDNF was reversed (P0.05), and the expression of PKA and p-CREB was reversed in alcohol-inhibited prefrontal cortex (P0.05) after administration of Rolipram (0. 5 and 1 mg/kg) for 28 days. Conclusion: ralopram, an inhibitor of phosphodiesterase 4, can significantly improve depression-like symptoms caused by alcoholism and abstinence, and alleviate alcoholism. The mechanism may be involved in the second messenger camp pathway. By inhibiting PDE4, Rolipram increased camp level in hippocampus and prefrontal cortex, and then activated PKA-CREB-BDNF pathway, which resulted in antidepressant effect.
【作者單位】： 浙江大學(xué)明州醫(yī)院;浙江醫(yī)藥高等�？茖W(xué)校;溫州醫(yī)科大學(xué);
【基金】：國(guó)家自然科學(xué)基金資助項(xiàng)目(No.81360195) 寧波市自然科學(xué)基金資助項(xiàng)目(No.2016A610239) 浙江醫(yī)藥高等專科學(xué)校科研項(xiàng)目(No.ZPCSR2016003)
【分類號(hào)】：R749.62

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本文編號(hào)：2106656