脂多糖连续注射诱发小鼠抑郁行为及认知改变

A Study on the Depressive Behavior and Cognitive Dysfunction Induced by Consecutive Injection of Lipopolysaccharide

目的观察脂多糖(lipopolysaccharide,LPS)连续注射5d后实验动物的抑郁样行为及学习认知的改变。方法用侧脑室定位技术对实验组C57小鼠连续注射LPS 5d,对照组小鼠注射相等体积的生理盐水。观察两组小鼠第2天的体质量,用糖水偏好实验、悬尾试验、旷场实验、高架十字迷宫实验、水迷宫实验等行为学实验检测实验小鼠行为学的改变。结果 1)第6天行为检测时,实验组小鼠较对照组小鼠体质量更轻,差异有统计学意义(t=6.24,df=14,P<0.001)。2)糖水偏好实验中,实验组小鼠糖水偏好百分比明显低于对照组,差异有统计学意义(t=9.48,df=14,P<0.01)。3)悬尾实验中,实验组小鼠悬尾不动时间明显高于对照组,差异有统计学意义(t=4.43,df=14,P<0.01)。4)旷场实验中,实验组小鼠在旷场中的活动路程(t=4.59,df=14,P<0.001)、直立次数(t=5.27,df=14,P<0.01)、活动次数(t=4.93,df=14,P<0.001)明显低于对照组。5)高架十字迷宫实验中,和对照组比较,实验组小鼠在闭臂停留的时间更短(t=4.10,df=14,P<0.01),在闭臂活动的速度更慢(t=12.84,df=14,P<0.001),差异均有统计学意义。6)水迷宫实验中,实验组小鼠在第2天的逃逸潜伏期较对照组明显增多,在第5天撤去平台后穿越目标象限的次数较对照组更少(t=4.18,df=14,P<0.001)。结论 LPS连续注射诱发了小鼠的抑郁样行为,且可影响实验小鼠的认知行为,是一个切实可行的抑郁模型,为慢性应激诱发的抑郁模型提供了更有力的支持,也为在此基础上抑郁的干预及调控提供了可能。

Objective To explore the depressive behavior and cognitive dysfunction after consecutive injection of lipopolysaccharide （LPS） for five days. Methods The lateral ventricular localization technique was used to give the consecutive injection for five days to the C57 mice in the experiment group with LPS and the mice in the control group with the same amount of normal saline. The body mass of those mice was observed and their behavioral changes were tested by the behavior tests including the sucrose preference test, tail suspension test, open field test, elevated plus-maze and Morris water maze. Results The body mass of the mice in the experiment group was significantly less than that of the mice in the control group on the 6th day of the behavioral tests（t^6.24, df= 14, P（0.001）. The mice in the experiment group showed less desire than those in the control group, and the differences were statistically significant in the sucrose preference test （t = 9.48, df= 14, P〈 0.01）. The tail suspension time of the experiment group was significantly longer than that of the control group in the tail suspension test（t=4.43, df=14, P〈0.01）. The mice of the experiment group behaved significantly worse than those of the control group in the distance of activity （t = 4.59, df = 14, P〈0. 001）, times of standing upright （t = 5.27, P〈 0.01） and times of activity（t= 4.93, dr= 14, P〈0. 001） in the open field test. The time of closed arm was significantly longer （t=4.10, df=14, P（0.01） and the speed was significantly lower（t=12.84, df=]4, P〈 0. 001） in the experiment group than in the control group in the elevated plus-maze. In the Morris water maze, the escape latency was elevated much more and the times of crossing the targeted quadrant were less in the experiment group than in the control group, and the differences were statistically significant （t=4.18, P〈0. 001）. Conclusion The consecutive injection of LPS induces the depressive-like behavior and affects the cognitive behavior of laboratory animals. It can also establish the depression model successfully, which can offer the strong support for the depression model induced by chronic stress and the potential to intervene and regulate depression.