目的 建立心理亚健康大鼠模型,并采用行为学、代谢组学、因子分析等方法对模型进行综合评价。方法 模拟人在竞争激烈的社会环境中因饮食不节、作息不规律、精神压力过大、社交失败所致的心理亚健康状态,采用非躯体复合因素即空瓶应激、旁观电击应激、饮食不节应激、昼夜不分应激、社交失败应激等建立心理亚健康大鼠模型。进行糖水偏爱、高架十字迷宫、明暗箱、旷场等行为学实验,观察大鼠体质量和脏器指数,同时采用基于行为学的因子分析和代谢组学对模型进行评价。结果 大鼠体质量和脏器指数未发生明显变化;但糖水偏爱率显著降低(P<0.05),在高架十字臂中的开臂次数比例和开臂时间比例明显减少(P<0.05),在避暗实验中错误次数及暗箱停留时间显著增加(P<0.05、0.01)。因子分析从宏观的行为学数据中挖掘出3个公因子:抑郁焦虑因子、记忆因子和其他因子。代谢组学分析显示,PLS-DA图中模型组和对照组沿t[1]轴明显分开,并确认高密度脂蛋白、醋酸、谷氨酸、肌酸、胆碱、甜菜碱和苏氨酸7种差异代谢产物。结论 建立的心理亚健康大鼠模型能够在一定程度上反映人类的心理亚健康状态,所用的评价方法科学合理、稳定可靠、可行性较好,可为其机制研究及相关药物作用机制研究提供依据。

Objective To establish the animal model of rat with psychological sub-health and carry out the comprehensive evaluation by the methods of behavior, metabonomics, and factor analysis. Methods Simulating human to cause the psychological sub-health state in the fierce competitive social environment due to improper diet, irregular work and rest, overload mental stress, and social failure. Modeling procedures by using composite and non-somatic stimuli factors including stimulation of empty bottle stress, on the sidelines of shock stress, improper diet stress, round-the-clock stress, and social failure stress. The following behavioral experiments were conducted such as sucrose preference rate, high plus maze, light/dark box, and open field test. Body mass and organ index were observed in rats. The factor analysis was used based on behavioral and metabolomic evaluate model. Results The body weight and organ index of rats did not change significantly; But sucrose preference rate decreased significantly (P<0.05), the number of open arms entries and the proportion of time in the open arms decreased significantly (P<0.01); Error count and the time into black box increased significantly (P<0.01). Factor analysis dug up three common factors from the macroscopic behaviors, namely depression and anxiety, memory, and other factors. Metabolomic analysis showed that the control group and model group clearly separated in the PLS-DA plot, and identified seven biomarkers: high density lipoprotein, acetic acid, glutamic acid, creatine, choline, betaine, and threonine. Conclusion The establishment of the rat model with psychological sub-health can reflect the state of psychological sub-health of human being. And the evaluation method of model possesses scientific rationality, feasibility, and reliablity. It can provide the reference for further study on its mechanism and the related drugs action.

国家自然科学基金资助项目(81441096);山西省科技创新重点团队(2013131015)