解郁安神颗粒对卒中后抑郁小鼠模型的抗抑郁作用

Effect of Jieyu Anshen Granule on Post-stroke Depression of Mouse Model

目的探讨解郁安神颗粒(JY)对卒中后抑郁(PSD)小鼠模型的抗抑郁作用。方法将雄性昆明种小鼠随机分为正常对照组、模型对照组、艾司西酞普兰组(5 mg·kg^(-1))及JY小、中、大剂量组(JY 0.75,1.50,3.00 g·kg^(-1)),每组12只。采用双侧颈总动脉线栓再灌注制备脑缺血小鼠模型,给予慢性不可预知性温和刺激制备PSD小鼠模型。艾司西酞普兰及JY灌胃给药,每天1次,连续给药28 d。通过悬尾实验及强迫游泳实验评价JY对PSD小鼠抑郁行为的影响。采用高效液相色谱法检测PSD小鼠海马去甲肾上腺素(NE)、多巴胺(DA)及5-羟色胺(5-HT)水平。采用Western blotting检测PSD小鼠海马5-羟色胺1A受体(5-HT1AR)表达。结果与正常对照组比较,模型对照组小鼠悬尾及游泳不动时间明显增加(P<0.05);与模型对照组比较,JY小、中、大剂量组小鼠悬尾及游泳不动时间明显减少(P<0.05或P<0.01)。与正常对照组比较,模型对照组小鼠海马NE、DA及5-HT水平均明显降低(P<0.05或P<0.01),海马5-HT1AR表达明显降低(P<0.05)。与模型对照组比较,JY小、中剂量组小鼠海马NE、DA及5-HT水平明显升高(P<0.05或P<0.01),海马5-HT1AR表达明显升高(P<0.05)。结论 JY对PSD小鼠模型具有抗抑郁作用,其作用机制可能与提高海马NE、DA及5-HT水平,以及上调海马5-HT1AR表达有关。

Objective To investigate the antidepressant effect of Jieyu Anshen granules(JY)on post-stroke depression(PSD)mouse model.Methods PSD mouse model was established by bilateral common carotid artery occlusion followed by chronic unpredictable mild stress.The mice were divided into six groups:normal control group,model control group,escitloapram group(5mg·kg^-1),low-,medium-and high-dose JY groups(JY0.75,1.50and3.00g·kg^-1),12per group.The tail suspension and forced swim tests were used to assess depression-like behaviors of mice.The levels of NE,DA and5-HT in hippocampus were measured by HPLC.The expression of hippocampal5-HT1A R was evaluated by western blotting.Results Compared with the normal control group,the suspension and swimming immobility time significantly increased(P<0.05).Compared with the model control group,the immobility time of PSD mice in the low-,medium-and high-dose JY groups in the model significantly reduced(P<0.05,P<0.01).Compared with the normal control group,the levels of hippocampal NE,DA and5-HT control group were decreased(P<0.05,P<0.01),and the expression of hippocampal5-HT1A R in the model control group was reduced(P<0.05).Compared with the model control group,the levels of hippocampal NE,DA and5-HT increased(P<0.05,P<0.01),and the expression of hippocampal5-HT1A R in medium-and high-dose JY groups.Conclusion JY has exerted antidepressant effect on PSD mouse model,which may be ascribed to the up-regulation of the level of NE,DA and5-HT,and the expression of hippocampal5-HT1A R.