抗抑郁药文拉法辛、氟西汀及米氮平的神经保护及神经营养作用研究  

Application of antidepressants: venlafaxine, fl uoxetine and mirtazapine in neuroprotection and neurotrophy

作　　者：陈嘉[1] 顾丰华[1] 赵绪韬[1] 刘翔[1] 董文心[1] 张渊[2] 

机构地区：[1]中国医药工业研究总院上海医药工业研究院创新药物与制药工艺国家重点实验室,上海200437 [2]上海交通大学附属第一人民医院药剂科,上海200080

出　　处：《世界临床药物》2015年第5期310-316,共7页World Clinical Drug

摘　　要：目的探讨文拉法辛、氟西汀及米氮平的抗抑郁作用及其与神经保护及神经营养的相关性。方法 1体内试验,选用CUMS大鼠模型,分析3种抗抑郁药物对脑内神经发生的影响[体重、糖水摄入量、双皮质素(DCX)阳性细胞数];2体外试验,以L-Glu,H2O2及地塞米松造成原代新生大鼠海马细胞损伤,评价文拉法辛、氟西汀及米氮平的神经保护作用(LDH释放率、海马细胞存活率);3采用基因芯片技术,在原代海马细胞中,分析文拉法辛、氟西汀及米氮平给药8 h细胞中神经营养素相关基因的表达水平。结果文拉法辛、氟西汀及米氮平虽均能不同程度改善CUMS刺激造成的糖水摄入比率的降低(P<0.05或P<0.01),但该作用促进神经发生无关(DCX阳性细胞均未增加);对不同应激损伤的大鼠海马细胞,文拉法辛、氟西汀及米氮平的效果存在差异;文拉法辛对于地塞米松及L-Glu所致细胞损伤具有显著改善(P<0.05),氟西汀对L-Glu及H2O2所致细胞损伤有显著改善(P<0.05),米氮平仅对H2O2所致细胞损伤有显著改善(P<0.05);在基因芯片测试中,以上三种抗抑郁药物虽都能提高脑内脑源性神经营养因子的表达水平,但对于其他神经营养素的作用则表现不一。结论抗抑郁药物可能通过神经保护作用阻止或逆转海马神经元的损伤及死亡,或促进神经发生的作用代替由于应激造成的神经元丢失发挥其治疗作用。Objective To investigate the neuroprotection and neurotrophic effects of antidepressants： venlafaxine, fluoxetine and mirtazapine. Methods 1. In vivo test, CUMS rats were treated with antidepressants for 7 weeks, the neurogenesis in dentate gyrus of hippocampus was measured. 2. In vitro test, the cultured neonate rat hippocampal neurons were treated by L-Glu, H2O2 and dexamethasone and then the protective effects of antidepressants to cultured rat hippocampal neurons in different stress condition were observed. 3. Through gene chip experiment, the mRNA levels of neurotrophins were measured in cultured neonate rat hippocampal neurons with venlafaxine, fluoxetine and mirtazapine. Results In vivo, venlafaxine, fluoxetine and mirtazapine could improve depression behavior induced by CUMS （P〈0.01 or P〈0.05）. However, venlafaxine, fluoxetine and mirtazapine did not show inducing neurogenesis effects on CUMS rats. In vitro, they had different protective effects on injured neonate rat hippocampal neurons. Venlafaxine could decrease evidently cell injury in the chronic L-Glu and dexamethason injury model （P〈0.05）. Fluoxetine could decrease evidently cell death rate in L-Glu and H2O2 model （P〈0.05）. Mirtazapine only antidepressants in this research could increase mRNA level levels of neurotrophins. Conclusion The neuroprotection and can involve distinctive mechanisms. protected cells from damaging by H202 （P〈0.05）. Although of BDNF, they had different effects on regulating the mRNA neurotrophic effects of venlafaxine, fluoxetine and mirtazapine

关 键 词：文拉法辛 氟西汀 米氮平 神经保护 神经营养素 

分 类 号：R971.43[医药卫生—药品]