阿米替林抗抑郁的免疫机制研究
Study on the antidepressant immunologic mechanisms of Amitriptyline
作者:郭英;徐娅娟;姚晓静;杨佳妮;和润杰;白宇凡;莫正纪;罗海芸;
Author:
收稿日期: 年卷(期)页码:2018,33(03):-242-244
期刊名称:华西药学杂志
Journal Name:WEST CHINA JOURNAL OF PHARMACEUTICAL SCIENCES
关键字:阿米替林;小胶质细胞;蛋白激酶B;白细胞介素1β;肿瘤坏死因子α;脑源性神经营养因子;抗抑郁;免疫机制
Key words:
基金项目:云南省科技厅-昆明医科大学联合专项(2017FE467-160);;
昆明医科大学大学生创新性实验项目(2017~2018)
中文摘要
目的探讨阿米替林通过对小胶质细胞的免疫调节来发挥抗抑郁作用的机制。方法利用脂多糖(LPS)刺激小胶质细胞,采用Western blot检测磷酸化蛋白激酶B(p-AKT)、蛋白激酶B(AKT)、核因子-κB(NF-κB)、白细胞介素1β(IL-1β)、肿瘤坏死因子α(TNF-α)及脑源性神经营养因子(BDNF)的蛋白表达;采用免疫荧光法检测IL-1β、TNF-α、BDNF的蛋白表达。结果阿米替林可降低被LPS激活的小胶质细胞中p-AKT/AKT、NF-κB、TNF-α、IL-1β的蛋白表达,增加BDNF的蛋白表达。结论阿米替林可能通过调控AKT/NF-κB信号通路,减少炎症因子TNF-α、IL-1β的释放,增加BDNF的蛋白表达,从而保护小胶质细胞,发挥抗抑郁作用。
参考文献
[1]Raz Y,Rimmerman N,Reshef R.Depression as a microglial disease[J].Trends Neurosci,2015,38(10):637-658.
[2]Yuan Y,Zha H,Rangarajan P,et al.Anti-inflammatory effects of Edaravone and Scutellarin in activated microglia in experimentally induced ischemia injury in rats and in BV-2 microglia[J].BMC Neurosci,2014,22(15):125-145.
[3]Vismari L,Alves GJ,MuscaráMN,et al.A possible role to nitric oxide in the anti-inflammatory effects of amitriptyline[J].Immunopharma Immunot,2012,34(4):578-585.
[4]Ginhoux F,Lim S,Hoeffel G,et al.Origin and differentiation of microglia[J].Front Cell Neurosci,2013,7:45.
[5]Lee HS,Kwon SH,Ham JE,et al.Zaprinast activates MAPKs,NF-κB,and Akt and induces the expressions of inflammatory genes in microglia[J].Int J Immunopharmacol,2012,13(3):232-241.
[6]O'Neill LA,Kaltschmidt C.NF-κB:A crucial transcription factor for glial and neuronal cell function[J].Trends Neurosci,1997,20(6):252-258.
[7]Hisaoka-Nakashima K,Kajitani N,Kaneko M,et al.Amitriptyline induces brain-derived neurotrophic factor(BDNF)mRNA expression through ERK-dependent modulation of multiple BDNF mRNA variants in primary cultured rat cortical astrocytes and microglia[J].Brain Res,2016,1634(1):57-67.
【关闭】