Fu Xiao-Yan, Li Hai-Yan, Jiang Qing-Song, Cui Ting, Jiang Xin-Hui, Zhou Qi-Xin, Qiu Hong-Mei
aKey Laboratory of Biochemistry and Molecular Pharmacology, Department of Pharmacology bKey Laboratory of Biochemistry and Molecular Pharmacology, Department of Drug Analysis, School of Pharmacy of Chongqing Medical University, Yixueyuan Lu, Chongqing, China.
Neuroreport. 2016 Sep 7;27(13):953-9. doi: 10.1097/WNR.0000000000000637.
In recent years, some studies have suggested that the activation of inflammatory system plays a role in the occurrence of depression. Tumor necrosis factor-α (TNF-α), as one of the preinflammatory cytokines, has been reported to be involved in the occurrence of various diseases including depression. Infliximab, an antagonist of TNF-α, is usually used to treat some autoimmune diseases such as Crohn's disease and can perhaps be used to treat other diseases. In this study, the antidepressant effect and a possible mechanism of infliximab were investigated by studying the depression-like behavior and expression of TNF-α, indoleamine 2, 3-dioxygenase (IDO), and 3-hydroxyl amino acid oxygenase (HAAO) from the cortex and hippocampus in rat exposed to chronic unpredicted stress. Forty male Sprague-Dawley rats were divided into a control group (CG), an infliximab-treated control group, a model group (MG), and an infliximab-treated model group (IFXM). Infliximab (5 mg/kg once week) was administered to the infliximab-treated control group and IFXM rats by an intraperitoneal injection, whereas an equivalent volume of vehicle was administered to CG and MG rats. Rat behaviors and the expression of TNF-α, IDO, and HAAO in the cortex and hippocampus were determined. It was found that a significant relief in depression-like behaviors was observed with a downregulation of TNF-α, IDO, and HAAO expression in the IFXM rats compared with MG rats. The results show the antidepressant effect of infliximab and suggest that its mechanism is partly related to inhibition of IDO-HAAO pathway activation mediated by TNF-α in rat brain.
近年来，一些研究表明炎症系统的激活在抑郁症的发生中起作用。肿瘤坏死因子-α（TNF-α）作为前炎症细胞因子之一，据报道参与包括抑郁症在内的各种疾病的发生。英夫利昔单抗是TNF-α的拮抗剂，通常用于治疗一些自身免疫性疾病，如克罗恩病，或许也可用于治疗其他疾病。在本研究中，通过研究暴露于慢性不可预测应激的大鼠的抑郁样行为以及皮质和海马中TNF-α、吲哚胺2,3-双加氧酶（IDO）和3-羟基氨基酸氧化酶（HAAO）的表达，来探究英夫利昔单抗的抗抑郁作用及其可能机制。40只雄性Sprague-Dawley大鼠被分为对照组（CG）、英夫利昔单抗处理的对照组、模型组（MG）和英夫利昔单抗处理的模型组（IFXM）。英夫利昔单抗处理的对照组和IFXM组大鼠通过腹腔注射给予英夫利昔单抗（5mg/kg，每周一次），而CG组和MG组大鼠给予等量的溶剂。测定大鼠行为以及皮质和海马中TNF-α、IDO和HAAO的表达。结果发现，与MG组大鼠相比，IFXM组大鼠的抑郁样行为显著缓解，且TNF-α、IDO和HAAO表达下调。结果显示了英夫利昔单抗的抗抑郁作用，并表明其机制部分与抑制大鼠脑中由TNF-α介导的IDO-HAAO途径激活有关。
