抑郁症与阿尔茨海默病共病小鼠模型造模方法探究

Exploration of Co-morbidity Methods for Mouse Models of Depression and Alzheimer's disease. CHEN Yan，ZHENG Hantao，ZHOU Xiaoru，Shi Taoyuan，JIA Ru，WANG Yulu（College of Pharmacy, Fujian University of Traditional Chinese Medicine, Fuzhou 350122, China）

关键词:  共病  动物模型  抑郁症  AD  糖水偏好实验  Morris水迷宫  

Key words:  co-morbidity  animal model  depression  Alzheimer"s disease  sucrose preference test  Morris water maze.

摘要:

目的 探索建立两种抑郁症与阿尔茨海默病（Alzheimer's disease, AD）共病小鼠模型。方法 昆明小鼠根据糖水偏嗜度随机分为正常对照组、抑郁阴性组、单抑郁阳性组、AD阴性组、单AD阳性组、抑郁诱导AD组、AD诱导抑郁组。正常对照组自由摄水进食，抑郁阴性组慢性不可预知应激（Chronic unpredictable stress, CUS）应激4周，单抑郁阳性组CUS应激6周，AD阴性组和单AD阳性组分别皮下注射D-半乳糖（D-gal）并灌胃氯化铝（AlCl3）给药7周、10周，抑郁诱导AD组CUS应激6周+D-gal并AlCl3给药7周，AD诱导抑郁组D-gal并AlCl3给药10周+CUS应激4周。糖水偏好测试和开场试验评估小鼠抑郁样行为，Morris水迷宫检测学习记忆能力。结果 与正常对照组比较，抑郁阴性组各指标无显著性差异，单抑郁阳性组、抑郁诱导AD组糖水偏嗜度和水平垂直活动得分明显下降；抑郁诱导AD组逃避潜伏期明显延长、目标象限停留时间显著减少，与单AD阳性组相当。与正常对照组比较，AD阴性组各指标无显著性差异，单AD阳性组、AD诱导抑郁组逃避潜伏期明显延长、目标象限停留时间和平台穿越次数显著减少；AD诱导抑郁组小鼠糖水偏嗜度和水平垂直活动得分均显著下降，与单抑郁阳性组相当。结论 抑郁诱导AD小鼠模型和AD诱导抑郁小鼠模型均可成功构建。

Abstract:

OBJECTIVE To establish co-morbidity mouse models of depression and Alzheimer's disease (AD). METHODS Kunming mice were randomly divided into normal group (Control), depression-negative control group (DepNG), depression group (Dep), AD-negative control group (ADNG), AD group, depression-Alzheimer's disease model group (Dep-AD), and Alzheimer's disease-depression model group (AD-Dep) according to the degree of sucrose preference. The control group was administered with water freely, DepNG and Dep groups were individual exposed to chronic unpredictable stress (CUS) for 4 or 6 weeks. Meanwhile, the ADNG group and the AD group were administered subcutaneously with D-galactose (D-gal) and intragastric aluminum chloride (AlCl3) for 7 weeks and 10 weeks, respectively. CUS stress for 6 weeks + D-gal and AlCl3 administration for 7 weeks in the Dep-AD group, and 10 weeks of D-gal and AlCl3 administration + 4 weeks of CUS stress in the AD-Dep group. Sucrose preference test and open-field test were used to assess depressive-like behaviour in mice, and Morris water maze test was used to detect learning memory ability. RESULTS Compared with the Control group, the DepNG group had no significant differences in related indicators, sucrose preference, horizontal and vertical scores were decreased significantly in Dep group and Dep-AD group, horizontal and vertical scores; In the Dep-AD group escape latency was increased and staying target quadrant time was decreased significantly, which were compared to the AD group; Compared with the Control group, there were no significant differences in the ADNG group, in the AD and AD-Dep groups escape latency was increased, staying target quadrant time and platform crossing times were decreased significantly ; In the AD-Dep group sucrose preference, horizontal and vertical scores were decreased significantly, which were compared to the Dep group. CONCLUSION Both Dep-AD model of mice and AD-Dep model of mice can be successfully established.