阿米替林抗抑郁的免疫机制研究

Study on the antidepressant immunologic mechanisms of Amitriptyline

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。

OBJECTIVE To investigate the antidepressant immunologic mechanism of Amitriptyline on microglia. METHODS The cell model with neuroinflammation were established by LPS stimulation. Expressions of p-AKT,AKT,NF-κB,IL-1β,TNF-α and BDNF protein in the microglia were determined by Western blot. IL-1β,TNF-α and BDNF protein in the microglia were observed by Immunofluorescence method. RESULTS The results showed that Amitriptyline pretreated with microglia decreased the expression of p-AKT/AKT,NF-ΚB,TNF-α,IL-1β protein and upregulated the protein expression of BDNF. CONCLUSION This study demonstrates that Amitriptyline may protect microglia through regulating AKT/NF-κB signal pathway,decreasing the release of TNF-α and IL-1β,and increasing the protein expression of BDNF,therefore,Amitriptyline plays a role in antidepressant.