帕罗西汀与阿米替林联用对卒中后抑郁大鼠额前皮质区与海马区的单胺类递质、脑源性神经营养因子水平的改变

目的探究帕罗西汀与阿米替林联用对脑卒中后抑郁(post-stroke depression,PSD)大鼠额前皮质区与海马区的单胺类递质、脑源性神经营养因子(brain-derived neurotrophic factor,BDNF)水平的影响.方法SD大鼠被分为4组,即对照组、PSD组、帕罗西汀(Par)组和帕罗西汀+阿米替林(Par+Ami)组.通过"线栓法"和慢性不可预见性温和刺激建立PSD大鼠模型.Par组灌胃给予帕罗西汀1.8 mg·kg^-1,Par+Ami组在Par基础上腹腔注射阿米替林10 mg·kg^-1,干预3w.分别在干预前、PSD建模后和干预后检测大鼠体质量、停止游泳的时间和蔗糖偏爱度.在干预后分别通过酶联免疫吸附实验、qPCR和Western blot检测额叶皮质和海马体5-羟色胺(5-hydroxytryptamine,5-HT)、去甲肾上腺素(norepinephrine,NE)、多巴胺(dopamine,DA)以及BDNF mRNA和蛋白的水平.结果建模前各组大鼠体质量、行为学指标、皮质和海马体5-HT、NE、DA以及BDNF mRNA和蛋白的水平比较差异均无统计学意义(P>0.05).建模后大鼠的体质量和蔗糖偏爱度显著降低,停止游泳的时间显著升高(P<0.05).干预后PSD组大鼠的体质量、蔗糖偏爱度、质和海马体5-HT、NE、DA以及BDNF mRNA和蛋白的水平显著低于对照组,停止游泳的时间显著高于对照组(P<0.05).Par组和Par+Ami组的大鼠的体质量、蔗糖偏爱度、质和海马体5-HT、NE、DA以及BDNF mRNA和蛋白的水平显著高于PSD组,停止游泳的时间显著低于PSD组(P<0.05).并且Par+Ami组的大鼠的体质量、蔗糖偏爱度、质和海马体5-HT、NE、DA以及BDNF mRNA和蛋白的水平显著高于Par组,停止游泳的时间显著低于Par组(P<0.05).结论帕罗西汀联合阿米替林可更有效的提高皮质和海马体中5-HT等单胺类神经递质的水平,缓解PSD大鼠模型的抑郁程度,并且可促进BDNF的水平,改善神经功能,提高对PSD的疗效和预后.

Combination of paroxetine and amitriptyline in the changes of monoamine neurotransmitters and brain-derived neurotrophic factors in the prefrontal cortex and hippocampus of post-stroke depression rats

Objective To explore the combination of paroxetine and amitriptyline for monoamine neurotransmitters and brain-derived neurotrophic factors(BDNF)in the prefrontal cortex and hippocampus of poststroke depression(PSD)rats.Factor,BDNF level of influence.Methods SD rats were divided into 4 groups,namely,control group,PSD group,paroxetine(Par)group and paroxetine+amitriptyline(Par+Ami)group.A PSD rat model was established by"wire plug"and chronic unpredictable mild stimulation.Par group was given paroxetine 1.8 mg·kg^-1by gavage.In the Par+Ami group,amitriptyline 10 mg·kg^-1was intraperitoneally injected on the basis of Par for 3 weeks.Rat body weight,time to stop swimming,and sucrose preference were measured before intervention,after PSD modeling,and after intervention.After intervention,enzyme-linked immunosorbent assay,qPCR and Western blot were used to detect frontal cortex and hippocampal serotonin(5-hydroxytryptamine,5-HT),norepinephrine(NE),dopamine(dopamine,DA).And the levels of BDNF mRNA and protein.Results There were no significant differences in body weight,behavioral index,cortical and hippocampal 5-HT,NE,DA and BDNF mRNA and protein levels between the groups before the modeling(P>0.05).After modeling,the body weight and sucrose preference of the rats were significantly reduced,and the time to stop swimming was significantly increased(P<0.05).After intervention,the body weight,sucrose preference,quality and hippocampus 5-HT,NE,DA and BDNF mRNA and protein levels were significantly lower in the PSD group than in the control group.The time to stop swimming was significantly higher than that in the control group(P<0.05).The body weight,sucrose preference,quality and hippocampus 5-HT,NE,DA and BDNF mRNA and protein levels in the Par group and Par+Ami group were significantly higher than those in the PSD group.The time to stop swimming was significantly lower than that in the PSD group(P<0.05).In the Par+Ami group,the body weight,sucrose preference,quality and hippocampus 5-HT,NE,DA and BDNF mRNA and protein levels were significantly higher than those in the Par group,and the time to stop swimming was significantly lower than that in the Par group(P<0.05).Conclusion Paroxetine combined with amitriptyline is more effective in increasing the levels of monoamine neurotransmitters such as 5-HT in the cortex and hippocampus,alleviating the degree of depression in the PSD rat model,and promoting BDNF levels and improving neurological function.Improve the efficacy arid prognosis of PSD.