腹外侧眶皮层中miR-200对慢性应激所致大鼠抑郁行为调控作用研究

发布时间：2018-05-08 22:26

  本文选题：抑郁症 + 腹外侧眶皮层(VLO)　； 参考：《神经解剖学杂志》2017年06期

【摘要】：目的:观察慢性不可预知温和应激(CUMS)模型大鼠腹外侧眶皮层(VLO)内miR-200和双特异性磷酸酶1(DUSP1)表达变化,并探讨VLO内注射miR-200模拟物对抑郁行为的调控作用及机制。方法:大鼠建立CUMS抑郁模型后分为5组:CUMS+miR-200模拟物组(VLO内注射20 pmol miR-200 mimic);CUMS+阴性对照组(VLO内注射20 pmol阴性对照siRNA);无应激+阴性对照组;无应激+miR-200模拟物组;CUMS+氟西汀(10 mg/kg/d)组。依次进行蔗糖偏爱测试、旷场实验、高架十字迷宫实验。Western Blot检测VLO内DUSP1、细胞外调节蛋白激酶(ERK)、pERK蛋白表达。结果:与无应激组比较,CUMS组大鼠体重降低(P0.0001)、蔗糖偏爱下降(P=0.008),VLO中miR-200表达减少(P0.0001),DUSP1表达增高(P=0.0054);与CUMS+阴性对照组比较,CUMS+miR-200模拟物组大鼠蔗糖偏爱率(P=0.028),开放臂进入时间(P=0.031)和进入次数(P0.0001)均升高,总活动距离不受影响;与CUMS+阴性对照组比较,CUMS+miR-200模拟物组VLO中DUSP1(P=0.046)和pERK(P=0.042)蛋白水平显著升高。结论:慢性应激性环境所致抑郁样行为与VLO内pERK下调有关,miR-200可直接下调VLO内DUSP1表达,提高pERK表达并最终改善抑郁症状。
[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.
【作者单位】： 西安医学院基础医学研究所;
【基金】：国家自然科学基金(81501175,81500063) 陕西省科技厅青年人才项目(2016JQ8043,2016JQ8049) 西安医学院博士启动金(2015DOC05,2015DOC12)
【分类号】：R749.4
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本文编号：1863363