欧前胡素抗抑郁作用及机制研究

目的探讨欧前胡素(IMP)的抗抑郁作用及其机制。方法采用产前束缚应激对孕后期♀鼠建立抑郁模型,将SD♂子代大鼠随机分为5组,每组8只。分别是正常组(CON)、模型组(PS)、阳性组(氟西汀5 mg·kg^-1·d^-1)、IMP低、高剂量组(15、30 mg·kg^-1·d^-1)。均采用灌胃给药,每天1次,连续给药4周。进行糖水偏好、强迫游泳、旷场实验行为学测试,ELISA法、实时定量PCR检测海马及前额叶皮层中5-HT的浓度、5-HTT和5-HT_1AR的mRNA表达量。结果 IMP给药4周后,与PS组相比,IMP组糖水偏好度明显上升,不动时间减少,穿越总格子数、穿越中间格子数、直立和理毛次数明显增加(P<0.05,P<0.01),5-HT的浓度及5-HT_1AR的mRNA表达明显升高(P<0.05,P<0.01),5-HTT mRNA的表达明显降低(P<0.05,P<0.01)。结论 IMP可明显改善PS♂子代抑郁样行为,具有抗抑郁作用,其机制可能与升高5-HT浓度及5-HT1A R mRNA的表达,降低5-HTT mRNA的表达有关。

Antidepressant effect and mechanism of imperatorin

Aim To investigate the antidepressant effect of imperatorin(IMP)and explore its mechanism.Methods The model of depression was established by prenatal stress(PS)on late pregnant mother,then male offspring rats were randomly divided into five groups:control,PS model,fluoxetine group(5mg·kg^-1),IMP(15,30mg·kg^-1).Sucrose preference test,forced swimming test,and open field test were used to evaluate the behavioral changes.5-hydroxytryptamine(5-HT)concentration,serotonin transporters(5-HTT)and5-HT1A receptor(5-HT1A R)mRNA expression in the hippocampus and frontal cortex were measured using an enzyme-linked immunosorbent assay and real-time PCR.Results Compared with PS group,the percentage of sucrose preference and the number of total crossings,center crossings,rearing,grooming and5-HT concentration significantly increased in IMP group(P<0.05,P<0.01).The immobility time was significantly reduced in IMP group compared with PS group(P<0.01).The5-HT concentration and5-HT1A R mRNA expressions of PS offspring rats significantly increased by the administration of IMP(P<0.05,P<0.01).And,the increased5-HTT mRNA markedly decreased in IMP group compared with PS group(P<0.05,P<0.01).Conclusions IMP can obviously improve rat behavior and show anti-depressant effect,which may relate to the5-HT concentration,5-HTT and5-HT1A R mRNA expression in hippocampus and prefrontal cortex.