以脑内神经递质失衡为特征的抑郁症大鼠模型的改良研究

Improvement of the Depression Rat Model Based on the Unbalance of Neurotransmitters in the Brain

目的:改良以脑内神经递质含量失衡为特征的抑郁症大鼠模型。方法:根据糖水消耗实验结果,把健康SD大鼠分成正常对照组、原模型组和改良模型组。改良模型组不安装套管,直接向左侧海马注射1μL浓度为8μg/μL的SCH23390,隔1天注射1次,共注射4次。原模型组通过套管,向左侧海马注射1μL浓度为2μg/μL的SCH23390,每注射2 d,休息1 d,反复3次,共注射6次。通过比较造模两周后大鼠体重和行为学(旷场试验、糖水消耗实验)差异,评价改良效果。比较大鼠两侧海马、大脑皮质内5-HT、5-HIAA、NE、DA、Ach E含量变化,评价改良模型的病理特征。结果:成模两周后,与正常对照组比较,改良模型组、原模型组大鼠体重、旷场实验结果极显著下降(P <0. 01),糖水偏爱率显著降低(P <0. 05);同原模型组比较,改良模型组上述指标无统计学意义(P> 0. 05)。提示改良模型能够造成大鼠抑郁状态,且抑郁程度与原抑郁症模型相同。同正常对照组比较,改良模型组双侧海马5-HT、NE含量极显著增加,5-HIAA含量极显著降低(P <0. 01); DA含量呈现下降趋势,Ach E含量呈现增加趋势,但均没有统计学意义(P> 0. 05)。大脑皮质中,5-HT、NE、Ach E含量呈现增加趋势,5-HIAA、DA含量呈下降趋势(P> 0. 05),表明改良模型基本符合抑郁症病理特征。结论:改良的造模方法为直接向左侧海马注射1μL浓度为8μg/μL的SCH23390,隔1天注射1次,共注射4次。经过有效性、病理特征观察,证明改良的模型方法有效,与原模型比较,不需要安装套管,减少了造模时间,且改良的模型可用于强迫游泳、水迷宫等实验,实现了改良的目的。

Objective:To improve the depression rat model with neurotransmitters disorder within brain.Methods:According to the results of the sucrose consumption test,the healthy rats were randomly divided into normal control group,original model group and improved model group.Without installing the injection tube,the improved model group was injected SCH23390 into the left hippocampus every 2 days and 4 times in total,the dose was 8μg/μL.The original model group was placed the injection tube.Through the tube,SCH23390 was given into the left hippocampus at the dose of 2μg/μL.The medicine was given for 2 days,followed by a one-day rest,and 6 times totally.2 weeks after the modeling,the improved effect was evaluated based on the difference of weight and behavior test(sucrose consumption and the open-field)of different groups.And the athological feature was observed by comparing the change of the content of the 5-HT,5-HIAA,NE,DA and AchE in the left and right hippocampus,as well as in the cerebral cortical.Results:2 weeks after modeling,the weight and the open-field results of the improved model group and the original model group significantly decreased compared to the normal control group(P<0.01),and the sucrose-preference rate decreasing was also significant(P<0.05).Compared with the original model group,the improved model group had no significant difference(P>0.05).It demonstrated that the improved method could make the rats suffer from depression,and the impact was as same as the original.Compared with the normal control group,the level of 5-HT and NE increased significantly and 5-HIAA decreased significantly(P<0.01)in the bilateral hippocampus.The decreasing of DA and the increasing of AchE had no statistical significance(P>0.05).In the cerebral cortical,the content of 5-HT,NE and AchE increased,the content of 5-HIAA and DA decreased,the change was not statically significant(P>0.05).It showed that the improved model group rates had the pathological features of the depression.Conclusion:The modified modeling approach of establishing the depression rat model was to inject the SCH23390 into the left hippocampus of the rat.The dose was 8μg/μL and the frequency was once every 2 days and 4 times in total.By observation of validity and pathological features,the effectiveness of the improved approach was demonstrated.Furthermore,the modeling time was reduced by cancelling the procedure of the tube installation,and the model could be tested by the forced swimming test or the water maze,which achieved the goal of improvement.