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  

Role of miR-200 in chronic unpredictable mild stress induced depression in ventrolateral orbital cortex of rat

作　　者：赵妍[1] 王爽[1] 郭玉芳[1] 张军峰[1] 徐浩[1] 

机构地区：[1]西安医学院基础医学研究所,西安710021

出　　处：《神经解剖学杂志》2017年第6期672-678,共7页Chinese Journal of Neuroanatomy

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)

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(P<0.0001)、蔗糖偏爱下降(P=0.008),VLO中miR-200表达减少(P<0.0001),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(P<0.0001)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。Objective ： Using the chronic unpredictable mild stress （CUMS） model of rat to observe the expression of miR-200 and dual specificity phosphatase 1 （ DUSP1 ） in the ventrolateral orbital cortex （VLO） and explore the regula- tory role of miR-200 in depression. Methods： After the establishment of the CUMS depression model of rat, the rats were divided into 5 groups ： CUMS ＋ miR-200 mimics （ intra-VLO administration with 20 pmol miR-200 mimic）, CUMS ＋ negative control （intra-VLO administration with 20 pmol negative siRNA）, nonstress ＋ miR-200 mimics, nonstress ＋ negative control, CUMS ＋ floxitine （ i. p. 10 mg/kg/d ）. The sucrose preference test, open field test, elevated-plus maze test were performed to assess the depressive behaviors in rats. The expression levels of DUSP1, ERK, pERK in VLO were determined by Western Blot. Results： Compared with the nonstress group, the body weight in the CUMS group were significantly decreased （ P 〈 0. 0001 ）, as well as the sucrose preference （ P = 0. 008 ）. The expression of miR-200 in the rat VLO was decreased in the CUMS rats （ P 〈 0.0001 ）, while the DUSP1 expression was increased in those rats （P = 0.0054）. Compared with the CUMS ＋ negative control group, the expression of DUSP1 （ P = 0. 046 ）and the pERK （ P = 0.042） was significantly increased in the VLO of CUMS ＋ miR-200 mimic group. Conclusion： The chronic stress induced depressive-like behaviors are associated with the decreased ERK phosphorylation in the rats VLO. The miR-200 may ameliorate the depressive behavior by downregulation of the DUSP1 expression and therefore enhance the ERK phosphorylation in the rats VLO.

关 键 词：抑郁症 腹外侧眶皮层(VLO) miR-200 双特异性磷酸酶1(DUSP1) 大鼠 

分 类 号：R749.4[医药卫生—神经病学与精神病学]