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腹外側(cè)眶皮層中miR-200對慢性應(yīng)激所致大鼠抑郁行為調(diào)控作用研究

發(fā)布時間:2018-05-08 22:26

  本文選題:抑郁癥 + 腹外側(cè)眶皮層(VLO); 參考:《神經(jīng)解剖學(xué)雜志》2017年06期


【摘要】:目的:觀察慢性不可預(yù)知溫和應(yīng)激(CUMS)模型大鼠腹外側(cè)眶皮層(VLO)內(nèi)miR-200和雙特異性磷酸酶1(DUSP1)表達變化,并探討VLO內(nèi)注射miR-200模擬物對抑郁行為的調(diào)控作用及機制。方法:大鼠建立CUMS抑郁模型后分為5組:CUMS+miR-200模擬物組(VLO內(nèi)注射20 pmol miR-200 mimic);CUMS+陰性對照組(VLO內(nèi)注射20 pmol陰性對照siRNA);無應(yīng)激+陰性對照組;無應(yīng)激+miR-200模擬物組;CUMS+氟西汀(10 mg/kg/d)組。依次進行蔗糖偏愛測試、曠場實驗、高架十字迷宮實驗。Western Blot檢測VLO內(nèi)DUSP1、細(xì)胞外調(diào)節(jié)蛋白激酶(ERK)、pERK蛋白表達。結(jié)果:與無應(yīng)激組比較,CUMS組大鼠體重降低(P0.0001)、蔗糖偏愛下降(P=0.008),VLO中miR-200表達減少(P0.0001),DUSP1表達增高(P=0.0054);與CUMS+陰性對照組比較,CUMS+miR-200模擬物組大鼠蔗糖偏愛率(P=0.028),開放臂進入時間(P=0.031)和進入次數(shù)(P0.0001)均升高,總活動距離不受影響;與CUMS+陰性對照組比較,CUMS+miR-200模擬物組VLO中DUSP1(P=0.046)和pERK(P=0.042)蛋白水平顯著升高。結(jié)論:慢性應(yīng)激性環(huán)境所致抑郁樣行為與VLO內(nèi)pERK下調(diào)有關(guān),miR-200可直接下調(diào)VLO內(nèi)DUSP1表達,提高pERK表達并最終改善抑郁癥狀。
[Abstract]:Aim: to observe the changes of miR-200 and bispecific phosphatase 1 (DUSP1) expression in ventrolateral orbital cortex (VLOL) of rats with chronic unpredictable mild stress (CUMS), and to investigate the regulatory effect and mechanism of miR-200 mimics injected into VLO on depressive behavior. Methods: CUMS depression model was established in rats. The rats were divided into 5 groups: CUMS negative control group (CUMS negative control group), non-stress negative control group and non-stress miR-200 mimic group (10 mg / kg / d) group. Sucrose preference test, open field test, elevated cross maze test. Western Blot were used to detect the expression of DUSP1 in VLO and the expression of ERKPERK protein in extracellular regulated protein kinase. Results: compared with the non-stress group, the rats in the CUMS group lost weight P 0.0001G, the sucrose preference decreased the expression of miR-200 in the P0. 008C VLO and the expression of DUSP1 increased. Compared with the CUMS negative control group, the sucrose preference rate of rats in the CUMS miR-200 mimic group was P0.028, and the open arm entry time (P0. 031). The number of times of entry (P0.0001) increased, The total activity distance was not affected, and the protein levels of DUSP1P0. 046 and PERKP0. 042) in VLO of CUMS miR-200 analogue group were significantly higher than those of CUMS negative control group. Conclusion: depression induced by chronic stress environment and down-regulation of pERK in VLO can directly down-regulate DUSP1 expression in VLO, increase pERK expression and ultimately improve depressive symptoms.
【作者單位】: 西安醫(yī)學(xué)院基礎(chǔ)醫(yī)學(xué)研究所;
【基金】:國家自然科學(xué)基金(81501175,81500063) 陜西省科技廳青年人才項目(2016JQ8043,2016JQ8049) 西安醫(yī)學(xué)院博士啟動金(2015DOC05,2015DOC12)
【分類號】:R749.4
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本文編號:1863363

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