围绝经期抑郁小鼠模型的建立及评估  

Establishment and evaluation of perimenopausal depression mouse model

作　　者：夏先锋 刘庆义[1] 李敏 尚超[3] 张梅奎[1] Xia Xianfeng;Liu Qingyi;Li Min;Shang Chao;Zhang Meikui(General Hospital of Chinese PIA,Beijing 100853,China;Shanxi University of Traditional Chinese Medicine,Xianyang 712046,China;Institute of Pharmacology and Toxicology,Academy of Military Medical Sciences,Beijing 100850,Chin)

机构地区：[1]中国人民解放军总医院,北京100853 [2]陕西中医药大学,咸阳712046 [3]军事医学科学院毒物药物研究所,北京100850

出　　处：《中华行为医学与脑科学杂志》2018年第7期655-660,共6页Chinese Journal of Behavioral Medicine and Brain Science

基　　金：国家科技支撑计划项目（2013BAH14F00）

摘　　要：目的探索运用慢性不可预见应激±睡眠剥夺±去势制造C57BL/6雌雄小鼠抑郁模型，观察该模型的行为学和神经内分泌的变化，为抗抑郁药物活性筛选提供依据。方法将40只小鼠随机分为假手术组（12只）、围绝经期组（14只）和模型组（14只）；采用睡眠剥夺±慢性不可预见应激±去势方法建立围绝经期抑郁小鼠模型；体质量和外观评分、旷场实验、新环境进食抑制实验、强迫游泳实验评估小鼠抑郁模型；Elisa检测小鼠血清雌二醇和皮质酮水平。结果（1）慢性不可预见应激±睡眠剥夺4周后，与假手术组[（21．48±0．79）g，（0．02±0．06）分，（93．02±6．17）％]、围绝经期组[（22．02±0．15）g，（0．06±0．09）分，（90．30±11．68）％]相比，模型组小鼠体质量[（20．16±1．03）g]较轻、外表评分[（0．39±0．04）分]较高和糖水偏爱度[（58．11±11．97）％]下降，均差异有统计学意义（P〈0．05）；（2）与围绝经期组、假手术组相比，模型组小鼠旷场实验的水平运动、垂直运动得分和中央格百分比、强迫游泳和悬尾实验不动状态潜伏期和不动状态持续时间百分率均差异有统计学意义（P〈0．05）；（3）与围绝经期组、假手术组相比，模型组小鼠新环境抑制摄食潜伏期、探索总时间和单次探索时长差异有统计学意义（P〈0．05）。（4）与假手术组[（46．16±7．72）pmol／ml，（320．77±23．19）ng／ml]、围绝经期组[（9．75±1．77）pmoL／ml，（386．42±37．58）ng／ml]相比，模型组小鼠血清雌二醇[（9．99±0．37）pmol／ml]降低、皮质酮[（426．31±105．01）ng／ml]升高，差异有统计学意义（P〈0．05）。结论C57BL／6雌雄小鼠卵巢摘除后，通过4周的慢性不可预见应激±睡眠剥夺，表现了抑郁样行为。Objective To establish depression model in female C57BL / 6 mice using chronic unpredictable stress ± sleep deprivation ± castration and observe the change of behavior and neuroendocrine of this model to provide basis for screening anti-depressant drugs. Methods To simulate the etiopathological mechanism of perimenopausal depression or depression symptoms, C57BL/6 female adult mice were exposed to chronic unpredictable stress ± sleep deprivation ± castration to establish perimenopausal depression model. The mice were randomly divided into perimenopausal group, model group, sham operation group, which of be- havioral and neuroendocrine differences were observed. Results （ 1 ） Compared with the sham operation group （ （ 21.48±0.79 ） g, （ 0.02± 0.06 ）, （ 93.02 ± 6.17 ） % ） and the perimenopausal group （ （ 22.02± 0.15 ） g, （0.06±0.09） score, （ 90.30± 11.68） % ）, the body weight （ （ 20.16± 1.03 ） g） , coat state score （0.39±0.04） and sucrose preference （ （ 58.11 ± 11.97 ） % ） in the model group had significant differences （ all P〈0.05 ）. （2） Compared with the perimenopausal group and sham operation group, the horizontal movement, the vertical movement score and the percentage of central cells in the open field experiment, the percentage of immobility state and immobility state in forced swimming and tail suspension experiment of model mice were all significantly different （P〈0.05）. （3） Compared with the perimenopausal group and the sham-operation group, the latent period of eating, the total time of exploration and single exploration in NSFT had significant difference （P〈0.05）. （4） Compared with the sham operation group （ （46.16±7.72） pmol/ml, （ 320.77±23.19 ） ng/ml）and the perimenopausal group （ （ 9.75 ± 1.77 ） pmol/iul, （ 386.42± 37.58 ） ng/ml ）, serum estradiol （ （ 9.99± 0.37）pmol/ml） were elevated and corticosterone （ （426.31± 105.01 ） ng/ml） were increased in the model gr

关 键 词：围绝经期抑郁 小鼠模型 抑郁症 行为学 神经内分泌 

分 类 号：R749.4[医药卫生—神经病学与精神病学] R-332[医药卫生—临床医学]