不同时程的氟西汀与艾司西酞普兰应用对大鼠抑郁样行为及海马齿状回神经发生的影响

Effects of Different Duration of Fluoxetine and Escitalopram Use on Depressivelike Behavior and Neurogenesis of Hippocampal Dentate Gyrus in Adult Rats

目的:考察氟西汀及艾司西酞普兰不同的使用时程对大鼠抑郁样行为及海马齿状回神经发生的影响。方法:96只SD大鼠采用随机数字表法随机分为12组:M1组到M12组。各组造模后分别腹腔注射不同时程的生理盐水(M2、M6、M10组)、氟西汀(M3、M7、M11组)及艾司西酞普兰(M4、M8、M12组)。1周后,M1、M2、M3、M4组行矿场实验及糖水偏好实验,荧光免疫双标方法检测海马齿状回BrdU阳性细胞及Nestin阳性细胞的表达。2周后,M5、M6、M7、M8组行相同操作。3周后,M9、M10、M11、M12组行相同操作。结果:在矿场实验中,M1组与M3组,M6组与M8组,M10组与M11组、M10组与M12组间10min总行程差异有统计学意义(P<0.05)。在糖水偏好实验中,M2组与M4组,M6组与M8组,M10组与M11组、M10组与M12组间糖水偏好率差异有统计学意义(P<0.05)。M1组与M3组,M2组与M4组,M5组与M7组,M5组与M8组,M9组与M12组、M10组与M11组间BrdU/Nestin双标阳性细胞百分比差异有统计学意义(P<0.05)。结论:氟西汀与艾司西酞普兰使用3周后均能改善大鼠抑郁样行为。艾司西酞普兰在治疗抑郁症方面起效时间更快,可能的原因之一便是对海马区神经再生的影响更快速,继而通过对相关通路的作用,改善抑郁行为。

Objective：To investigate the effects of different duration of fluoxetine and escitalopram use on depressive-like behavior and neurogenesis of hippocampal dentate gyrus in adult rats.Methods：Ninety-six SD rats were randomly divided into twelve groups：from M1 group to M12 group.After subjected to CUMS,every group was injected with saline（M2group,M6 group and M10group）,or fluoxetine（M3group,M7 group and M11group）,or escitalopram（M4group,M8 group and M12group）for different duration respectively.After one week of intervention,the open-field test and 1% sucrose preference test were performed to observe the rats＇ depression-like behaviors for M1 group,M2group,M3 group and M4 group.After behavior test,theBrdU and Nestin positive cells of dentate gyrus in rats were detected by double-labeling immunofluorescence method.After two weeks of intervention,M5 group,M6group,M7 group and M8 group underwent the same operation.After three weeks of intervention,M9 group,M10group,M11 group and M12 group underwent the same operation.Results：In the open-field test,the difference of 10 minutes total moved distances were statistically significant（P〈0.05）between these groups：M1group vs M3 group,M6group vs M8 group,M10group vs M11 group,M10group vs M12 group.In the 1% sucrose preference test,the sucrose preference consumption differences were statistically significant（P〈 0.05）between these groups：M2group vs M4 group,M6group vs M8 group,M10group vs M11 group,M10group vs M12 group.There were significant differences（P〈0.05）in BrdU/Nestin positive cells percent between these groups：M1group vs M3 group,M2group vs M4 group,M5group vs M7 group,M5group vs M8 group,M9group vs M12 group,M10group vs M11 group.Conclusion：Three weeks of fluoxetine and escitalopram use can improve depression-like behavior in rats.Compared with fluoxetine,escitalopram reveales shorter onset time in the treatment of depression.One of the possible reasons is that it advances hippocampal neurogenesis quickly,then improves depressive behavior by the action of the relevant pathways.