不同应激方法建立焦虑大鼠模型的研究

目的：从不同时间点比较几种不同的应激方法建立焦虑大鼠模型的生物学特点，为寻找最合适的造模方法提供实验依据。方法：70只大鼠随机分为正常组、空瓶应激组、慢性情绪应激（CES）组、束缚应激3 h组、束缚应激6 h组，分别进行造模，于实验第7 d、14 d、21 d分别采用高架十字迷宫和场景恐惧测试测定大鼠的焦虑样行为，旷场测试考察大鼠的焦虑或抑郁样行为，强迫游泳实验测定大鼠的抑郁样行为，采用Elisa试剂盒检测大鼠海马组织中5-HT、DA含量。结果：焦虑样行为学测试结果表明，第14 d起，空瓶应激组、CES组、束缚应激6 h组大鼠开始产生焦虑样行为，此后焦虑样行为愈发明显，强迫游泳实验结果表明，束缚6 h组大鼠的不动时间于第7 d起即显著增加（P＜0.05）。同时，与正常大鼠比较，空瓶应激组和CES组大鼠海马5-HT、DA含量于第14 d开始显著上升（P＜0.05或P＜0.01）。结论：在上述几种焦虑模型中，束缚应激3 h焦虑样行为不明显；束缚应激6 h可能由于应激时间过长，表现出抑郁样行为。空瓶应激和CES能成功建立焦虑大鼠模型，且其焦虑行为表征有一定差异，可根据不同的实验目的选择对应的模型方法。

Research of Different Stress Methods to Establish Rat Models of Anxiety

Objective: To compare biological characteristics from several different stress methods to establish rat model of anxiety in different time points, providing experimental evidence for the most appropriate modeling methods. Methods: 60 rats were randomly divided into normal, empty bottle stress, chronic emotional stress (CES) group, restraint stress for 3h, 6h, and modeling respectively. In the experimental 7 d, 14 d, 21 d, elevated plus maze and fear condition system was used to test anxiety-like behavior in rats, open field test to study anxiety or depression-like behavior, forced swimming test was used to detect depression-like behavior in rats, and using the Elisa test kit to detect the contents of 5-HT, DA in the hippocampus in rats. Results: Anxiety-like behavioral test results showed that rats in empty bottle stress, CES, 6h restraint stress group started to have anxiety-like behavior since 14 d, then anxiety-like behavior was becoming increasingly apparent. Forced swimming test results showed that immobility time in 6 h restraint rats was significantly increased in the first 7 d(P <0.05). Meanwhile, compared with control group, hippocampal 5-HT, DA contents in empty bottle stress and CES rats increased significantly since 14 d. Conclusions: Among several stress methods established anxiety model, anxiety-like behavior in 3h restraint stress was not obvious; 6h restraint stress exhibited a depression-like behavior in the forced swimming test might be due to prolonged stress. Empty bottle stress and CES could successfully establish rat model of anxiety, and some differences were existed in its characterization of anxious behavior, then corresponding model approach could be selected according to different experimental purpose.