间断睡眠剥夺联合慢性不可预知温和刺激建立大鼠抑郁症模型的实验研究  

Experimental study on the establishment of a rat depression model by intermittent sleep deprivation combined with chronic unpredictable mild stress

作　　者：萧文云登 朱婧煊 陈志宇 XIAO Wen-yun-deng;ZHU Jing-xuan;CHEN Zhi-yu(Department of Prosthodontics,Stomatology Hospital of Hebei Medical University/Hebei Key Laboratory of Stomatology Hebei Clinical Medical Research Centre for Oral Diseases,Shijiazhuang 050017,China;Stomatology Class of 2020,Stomatology Hospital of Hebei Medical University,Shijiazhuang 050017,China)

机构地区：[1]河北医科大学口腔医学院口腔医院修复科,河北省口腔医学重点实验室,河北省口腔疾病临床医学研究中心,河北石家庄050017 [2]河北医科大学口腔医学院,河北石家庄050017

出　　处：《河北医科大学学报》2024年第11期1295-1300,共6页Journal of Hebei Medical University

基　　金：河北省自然科学基金基础研究专项(面上项目)(H2023206455);河北省高等学校科学技术研究青年基金项目(QN2022171)。

摘　　要：目的采用间断性慢性睡眠剥夺联合慢性不可预知温和刺激(chronic unpredictable mild stress,CUMS)的方法建立抑郁症失眠大鼠模型,并与传统单纯CUMS造模效果进行比较,探索更优的抑郁症造模方法。方法选取36只6~8周龄Sprague-Dawley大鼠,适应性喂养1周后随机均分为3组,A组,空白对照组;B组,CUMS组;C组,间断睡眠剥夺+CUMS组,每组12只。各组按照不同的抑郁症造模流程处理,造模时间为15 d,造模结束后进行行为学测试,ELISA法检测大鼠下丘脑中5-羟色胺(5-hydroxytryptamine,5-HT)、多巴胺(dopamine,DA)及去甲肾上腺素(norepinephrine,NE)浓度。结果间断睡眠剥夺+CUMS组第7天和第14天时体重增长率小于空白对照组和CUMS组,糖水偏好率小于空白对照组和CUMS组,不动时间长于空白对照组和CUMS组,穿越格数和站立次数少于空白对照组和CUMS组(P<0.05)。CUMS组和间断睡眠剥夺+CUMS组大鼠下丘脑5-HT浓度低于空白对照组,间断睡眠剥夺+CUMS组大鼠DA浓度低于空白对照组,NE浓度低于空白对照组和CUMS组(P<0.05)。结论采用为期15 d的CUMS联合间隔时间为1 d的20 h睡眠剥夺能够快速建立稳定的SD大鼠抑郁模型,与单纯CUMS造模方法比较在行为学表现方面效果更加明显,在造模时长方面优势显著。Objective To establish a rat model of insomnia caused by depression by using intermittent chronic sleep deprivation combined with chronic unpredictable mild stress(CUMS),and to compare the effect of CUMS with that of traditional CUMS alone,in order to explore a better modelling method for depression.Methods Thirty-six Sprague-Dawley rats aged 6-8 weeks were selected and randomly divided into three groups after 1 week of adaptive feeding:Group A,blank control group;Group B,CUMS group;and Group C,intermittent sleep deprivation+CUMS group,with 12 rats in each group.Each group was treated according to different depression modelling procedures,and the duration of modelling was 15 d.Behavioural tests were performed at the end of the modelling,and the concentrations of 5-hydroxytryptamine(5-HT),dopamine(DA)and norepinephrine(NE)in the hypothalamus of rats were detected by ELISA method.Results The intermittent sleep deprivation+CUMS group had a smaller body weight growth rate than the blank control and CUMS groups at 7 d and 14 d,a smaller sugar water preference rate than the blank control and CUMS groups,a longer immobility time than the blank control and CUMS groups,and a smaller number of traversing frames and standing than the blank control and CUMS groups(P<0.05).In the CUMS group and the intermittent sleep deprivation+CUMS group,the hypothalamic 5-HT concentration of rats was lower than that of the blank control group,the DA concentration of rats in the intermittent sleep deprivation+CUMS group was lower than that of the blank control group,and the NE concentration of rats in the intermittent sleep deprivation+CUMS group was lower than that of the blank control group and the CUMS group(P<0.05).Conclusion The use of 15-d CUMS combined with 20-h sleep deprivation at 1-d intervals can rapidly establish a stable depression model in SD rats,which has a more obvious effect on behavioural performance than CUMS alone,and has a significant advantage in terms of modelling duration.

关 键 词：抑郁症 睡眠剥夺 模型 动物 

分 类 号：R749.42[医药卫生—神经病学与精神病学]