目的 建立大鼠慢性应激抑郁模型并观察其胃肠黏膜组织的病理学变化规律。方法 采用慢性不可预见性应激的方法,将12只大鼠随机分为对照组和模型组,每组6只。对照组正常饲养,模型组采用10种应激方法,包括禁食24 h、禁水24 h、夹尾(距大鼠尾根部1 cm处)5 min、昼夜颠倒24 h、4 ℃冷水游泳5 min、45 ℃环境5 min、潮湿垫料24 h、倾斜45° 24 h、行为束缚4 h、水平震荡60次/min ,45 min,28 d内随机交替处理,每天一种方法,且相同的刺激至少间隔7 d以上。造模前后记录大鼠的体重,并于造模后依次进行旷场实验、强迫游泳实验和糖水偏爱实验等行为学评估,最后脱臼处死,并收集胃、回肠、盲肠、结肠等组织,包被切片后进行HE染色。结果 与对照组相比,模型组大鼠体重显著降低(P=0.0064)、穿越次数显著减少(P=0.0001)、直立次数显著减少(P=0.0007)、理毛次数显著减少(P=0.0011)、强迫游泳不动时间显著延长(P=0.000006)、糖水偏爱显著降低(P=0.008152);病理结果显示,造模后大鼠胃黏膜及肠道微绒毛结构破损严重,细胞核轻微固缩且深染。结论 慢性不可预见性多种应激组合的方法可成功建立大鼠抑郁模型,组织学显示这种抑郁状态可明显损害胃肠黏膜。

Objective To establish the rat chronic stress depression model and observe its gastrointestinal mucosa change rularity. To study the feasibility of establishing the chronic stress depression model based on chronic unpredictable stress method followed by behavioral evaluation, and further observe the histopathological changes in stomach, ileum, cecum and colon using HE staining. Methods The based method of chronic unpredictable stress was used. A total of 12 healthy male rats were randomly divided into two groups: control group and model group, six in each group. Rats in control group were regularly raised, and those in model group were randomly and alternately treated in 28 days with 10 stress methods, such as fasting for 24 h, water deprivation for 24 h, tail nipping (1 cm of rat tail head) for 5min, day and night inversion for 24 h, 4 ℃-cold water swimming for 5min, 45℃ environment for 5min, damp bedding for 24 h, sloping 45° for 24 h, behavior constraint for 4 h, horizontal vibrating (60 times/min) for 45 min. One method was chosen in each day and the interval of the same stimulation exceeded 7 days at least. Then, the rat body weight was recorded and the rats were on open field test, forced swimming test, and sugar water preference test. Finally, rats were dislocated and samples of stomach, ileum, cecum and colon were collected, and sliced and Haematoxylin and eosin staining was performed. Results Compared with the control group, the rat body weight significantly decreased (P=0.0064), the number of passing through significantly decreased (P=0.0001), the number of upright standing significantly decreased (P=0.0007), the number of grooming significantly decreased (P=0.0011), the no moving time in forced swimming significantly prolonged (P=0.000006) and sugar water preference significantly decreased(P=0.008152). Furthermore, the gastric mucosa and the microvilli in intestinal tract were seriously damaged, and nuclei slightly contracted and deeply stained. Conclusions Multiple chronic unpredictable stress method combination can correctly establish the rat chronic stress depression model, and the histology results demonstrate that the stress causes a signifcant damage in gastrointestinal mucosa.