1.湖南中医药大学科技创新中心,长沙 410208; 2. 山东省药学科学院,济南 250013
1.Science and Technology Innovation Center, Hunan University of Chinese Medicine, Changsha 410208, China. 2. Shandong Academy of Pharmaceutical Sciences, Jinan 250013
目的 采用慢性不可预见性中度应激联合快速和慢性改良多平台水环境睡眠剥夺的方法复制抑郁症失眠大鼠模型,对两种造模方法比较,选择最佳造模方式。 方法 84 只大鼠按体重随机分为空白组、环境对照组、慢性应激组、72 h 睡眠剥夺组、慢性应激 + 72 h 睡眠剥夺组、21 d 睡眠剥夺组、慢性应激 + 21 d 睡眠剥夺组,共 7 组,每组 12 只。 应激造模 14 d 和复合造模结束后进行行为学测试大鼠抑郁失眠样行为,ELISA 法检测大鼠血清中促肾上腺皮质激素释放激素(CRH)、促肾上腺皮质激素(ACTH)、皮质酮(CORT)的含量以及下丘脑中谷氨酸 (Glu)、γ-氨基丁酸(GABA)含量,HPLC-ECD 测定大鼠下丘脑中 NE、5-HT、DA 含量。 HE 染色观察各组大鼠下丘 脑的病理变化。 结果 与空白组相比,CUMS + 72 h SD 组和 CUMS + 21 d SD 组大鼠均表现出体重增长率和摄食量显著下降,旷场实验中自主活动次数明显减少,粪便粒数增多,不动时间显著增长,糖水消耗率显著减少,睡眠潜 伏期延长,睡眠时长明显缩短,其中后者表现更为显著;CUMS + 21 d SD 组大鼠血清中 CRH、ACTH、CORT 含量也明显升高,下丘脑中 Glu 含量显著增加、GABA 含量显著减少,单胺递质含量降低,下丘脑神经元细胞排列紊乱、间隙变大、空泡样性状显著。 结论 采用慢性不可预见性中度应激联合每天 18 h,连续 21 d 的改良多平台水环境睡眠剥夺的方法可稳定复制抑郁症失眠大鼠模型。
Objective The method of chronic unpredictable moderate stress combined with rapid and chronic improvement of multi platform water environment sleep deprivation was used to duplicate the rats model of depressive insomnia. Methods 84 Sprague Dawley rats were randomly divided into blank control group, environmental control group, chronic unpredictable moderate stress group (CUMS), 72 h sleep deprivation group ( 72 h SD), chronic unpredictable moderate stress + 72 h sleep deprivation group (CUMS + 72 h SD), 21 days sleep deprivation group (21 d SD), chronic unpredictable moderate stress + 21 days sleep deprivation group (CUMS + 21 d SD), 7 groups, 12 in each group. Weight measurement and food consumption statistics were conducted weekly. Behavioral tests in rats after 14 days of stress modeling and the end of compound modeling were carried out to test the depression and insomnia like behavior of rats. The contents of CRH, ACTH, CORT, Glu, GABA in hypothalamus were detected by ELISA. The contents of NE, 5-HT and DA in hypothalamus of rats were determined by HPLC-ECD. HE staining was used to observe the pathological changes of hypothalamus. Results Compared with the blank control group, CUMS + 72 h SD group and CUMS + 21 d group showed a significant decrease in body weight growth rate and food intake, a significant decrease in the number of autonomous activities, an increase in fecal particles, a significant increase in immobility time in forced swimming, a significant decrease in sugar water consumption, an increase in sleep latency, and a significant reduction in sleep duration, especially in CUMS + 21 d. The contents of CRH, ACTH and CORT in serum, Glu and GABA in hypothalamus were abnormal, contents of monoamine transmitters in hypothalamus were significantly decreased, the arrangement of neurons in hypothalamus was disordered, the gap was enlarged, and the vacuole shape was significant. Conclusions The rat model of depressive insomnia can be duplicated stably by using the method of chronic unpredictable moderate stress combined with sleep deprivation of multi platform water environment for 21 consecutive days.
黄会珍,赵洪庆,王宇红,张尚霞,金狮,罗薇絮,李姿蓉.抑郁症失眠大鼠模型的构建与评价[J].中国实验动物学报,2021,29(3):323~331.
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