本文選題：氟西汀 + 抑郁�。� 參考：《中國病理生理雜志》2016年09期

【摘要】：目的:探究氟西汀(fluoxetine)對(duì)慢性不可預(yù)見性溫和刺激(chronic unpredictable mild stress,CUMS)抑郁大鼠海馬突觸重塑的m TOR和細(xì)胞自噬信號(hào)調(diào)控作用。方法:60只雄性Sprague-Dawley大鼠隨機(jī)分成正常對(duì)照(control)組、CUMS組和氟西汀組。采用CUMS結(jié)合孤養(yǎng)法構(gòu)建CUMS抑郁模型,期間給予氟西汀(20 mg·kg-1·d-1)灌胃治療。通過體重變化、糖水測試水平及行為學(xué)實(shí)驗(yàn)驗(yàn)證模型建立,采用RT-PCR和Western blotting等生化方法測定突觸重塑相關(guān)蛋白膠質(zhì)纖維酸性蛋白(glial fibrillary acidic protein,GFAP)、突觸泡蛋白(synaptophysin,SYP),細(xì)胞凋亡相關(guān)蛋白Bcl-2、cleaved caspase-3,m TOR信號(hào)通路相關(guān)蛋白m TOR、4EBP1,自噬相關(guān)蛋白beclin 1、LC3 mRNA及蛋白表達(dá)水平的變化。結(jié)果:與control組相比,CUMS大鼠的體重、糖水?dāng)z取量、曠場實(shí)驗(yàn)總路程和中間停留時(shí)間均下降,差異具有統(tǒng)計(jì)學(xué)顯著性。RT-PCR和Western blotting實(shí)驗(yàn)結(jié)果顯示,與control組相比,CUMS組SYP和GFAP的mRNA和蛋白水平顯著下調(diào),Bcl-2表達(dá)下調(diào),cleaved caspases-3上調(diào),m TOR及下游靶分子4EBP1磷酸化水平下調(diào),細(xì)胞自噬關(guān)鍵基因beclin1和LC3在mRNA和蛋白水平顯著上調(diào)。氟西汀可以減緩以上結(jié)果中的上調(diào)或下調(diào)趨勢,差異具有統(tǒng)計(jì)學(xué)顯著性。結(jié)論:氟西汀可能通過下調(diào)細(xì)胞凋亡和自噬信號(hào)通路以及上調(diào)m TOR信號(hào)通路調(diào)節(jié)海馬突觸重塑并緩解抑郁癥狀。
[Abstract]:Aim: to investigate the effects of fluoxetine on m TOR and autophagy signal regulation of hippocampal synaptic remodeling in chronic unpredictable mild stimulation of chronic unpredictable mild stress CUMS in depression rats. Methods 60 male Sprague-Dawley rats were randomly divided into control group and fluoxetine group. The depression model of CUMS was established by CUMS combined with solitary therapy, during which 20 mg kg-1 d -1 of fluoxetine was administered intragastric. The model was established by weight change, sugar water test level and behavioral experiment. RT-PCR and Western blotting methods were used to detect synaptic remodeling associated protein glial fibrillary acidic protein RT-PCR, synaptophysin Sysp, apoptosis-associated protein Bcl-2caspase-3caspase-3 TOR signaling pathway related protein m TOR4EBP1, autophagy associated protein beclin 1LC3 mRNA, and autophagy associated protein beclin 1LC3 mRNA. Changes in protein expression levels. Results: compared with the control group, the body weight, the intake of sugar water, the total distance and the middle residence time of the open field experiment were all decreased. The difference was statistically significant. The results of RT-PCR and Western blotting experiment showed that there was no significant difference between the two groups. Compared with control group, the mRNA and protein levels of SYP and GFAP in Cucms group were significantly down-regulated. The expression of Bcl-2 was down-regulated, and the expression of caspases-3 was down-regulated, and the phosphorylation level of 4EBP1 was down-regulated, and the key genes beclin1 and LC3 of autophagy were up-regulated in mRNA and protein levels. Fluoxetine can slow down the upward or downward trend of the above results, the difference is statistically significant. Conclusion: fluoxetine may regulate hippocampal synaptic remodeling and alleviate depression by down-regulating apoptosis and autophagy signaling pathway and up-regulating m TOR signaling pathway.
【作者單位】： 嘉興學(xué)院醫(yī)學(xué)院;
【基金】：浙江省實(shí)驗(yàn)動(dòng)物科技計(jì)劃項(xiàng)目(No.2014C37019) 嘉興市科技局項(xiàng)目(No.2015AY23066)
【分類號(hào)】：R749.4

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本文編號(hào)：1811986