【作者】 苏芬丽； 高维； 涂继莹； 李焕德；

【机构】 广州中医药大学第一附属医院药剂科； 中南大学湘雅二医院临床药学研究室；

【摘要】 目的应用代谢物组学的方法研究文拉法辛治疗抑郁症的生化机制,观察药物对大鼠脑内神经递质代谢变化的影响。方法结合分养与慢性不可预见应激的方法造成大鼠抑郁模型,应用LC-MS/MS观察大鼠脑组织中单胺类神经递质及其代谢产物的变化,采用线性判别分析与主成分分析方法判别代谢产物谱的变化。结果抑郁模型大鼠灌服文拉法辛后,中、高剂量的文拉法辛能显著增加脑内5-HT和NE的含量,并能使DA的含量也有一定程度升高,且均比氟西汀引起的神经递质改变要明显。结论文拉法辛可以从多方面来调节中枢单胺类神经递质之间的关系,通过抑制5-HT、NE再摄取,同时降低二者的代谢,纠正递质代谢紊乱,提高其含量,并能协调5-HT、NE及DA间的平衡,以达到抗抑郁的功能。更多还原

【Abstract】 Objectives To study the biochemical mechanism of venlafaxine through determining the metabolism of monoamine neurotransmitters in brain tissues of rat model of depression after administration of venlafaxine using metabonomic method.Methods The rat model of depression was established by using the methods of separation and chronic unpredictable stress.The changes of monoamine neurotransmitters and their metabolites in rat brain tissue were determined by LC-MS/MS.Linear discriminant analysis(LDA)and principal components analysis(PCA)were used in data analysis of metabonomic.Results Compared with saline,venlafaxine could significantly increase brain 5-HT and NE levels at middle dose(16 mg·kg-1)or high dose(32 mg·kg-1),especially at middle dose.These increases were greater than those seen with the comparable dose of SSRI,fluoxetine,under the same experimental conditions.Conclusions Venlafaxine lower brain neurotransmitter metabolite levels by decreasing brain neurotransmitters turnover.Venlafaxine could correct the disorder of neurotransmitters’ metabolism and coordinate the balance of 5-HT,NE and DA to reach the anti-depressed function.更多还原