目的 采用脂多糖（lipopolysaccharide，LPS）诱导的小鼠抑郁样模型，探究逍遥散拆方药队（柴胡、当归、薄荷，CDB）挥发油部位的抗抑郁作用，及对磷脂酰肌醇3-激酶（phosphatidylinositol 3-kinase，PI3K）/蛋白激酶（protein kinase B，Akt）/核因子E2相关因子2（nuclear factor erythroid 2-related factor 2，Nrf2）信号通路的影响。方法 雄性C57BL/6J小鼠按体质量分层随机分为对照组、模型组、盐酸氟西汀（10 mg/kg）组和CDB挥发油高、低剂量（73.6、36.8 mg/kg）组。小鼠连续ig给药16 d，给药第13～15天，ip 1 mg/kg LPS（20 mL/kg）建立模型。通过糖水偏好测试、强迫游泳实验和悬尾实验观察动物抑郁样行为；ELISA法检测小鼠血清白细胞介素-1β（interleukin-1β，IL-1β）、肿瘤坏死因子-α（tumor necrosis factor-α，TNF-α）水平；化学法检测小鼠海马组织丙二醛（malondialdehyde，MDA）、谷胱甘肽（glutathione，GSH）水平和超氧化物歧化酶（superoxide dismutase，SOD）活性；尼氏染色法检测小鼠海马尼氏小体数量；免疫荧光法检测小鼠海马CA3区离子钙结合衔接分子-1（ionized calcium-binding adapter molecule-1，Iba-1）表达；Western blotting检测小鼠海马脑源性神经营养因子（brain-derived neurotrophic factor，BDNF）、p-PI3K/PI3K、p-Akt/Akt、Nrf2、血红素加氧酶-1（heme oxygenase-1，HO-1）、SOD1、p-p65/p65、IL-1β、Iba-1蛋白表达。结果 CDB挥发油显著提高模型小鼠糖水偏好率（P＜0.01），缩短强迫游泳和悬尾实验不动时间（P＜0.05、0.01）；显著降低海马MDA水平（P＜0.05），提高GSH水平及SOD活性（P＜0.05），降低血清IL-1β和TNF-α水平（P＜0.01）；显著增加小鼠海马CA3区尼氏小体平均荧光强度并抑制CA3区Iba-1表达（P＜0.05、0.01）；显著上调海马组织BDNF、p-PI3K/PI3K、p-Akt/Akt、Nrf2、HO-1和SOD1表达水平（P＜0.05、0.01），抑制p-p65/p65、IL-1β、Iba-1蛋白表达（P＜0.05、0.01）。结论 CDB挥发油能激活PI3K/Akt/Nrf2信号通路，提高抗氧化水平并减轻神经炎症，从而发挥抗抑郁作用。

Objective Using lipopolysaccharide (LPS) to induce a depression-like model in mice to investigate the antidepressant effects of volatile oil parts of disassembled prescription [Chaihu (Bupleuri Radix), Danggui (Angelicae Sinensis Radix), Bohe (Menthae Haplocalycis Herba), CDB] of Xiaoyao San (逍遥散) and its effects on phosphatidylinositol 3-kinase (PI3K)/ protein kinase B (Akt)/nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway. Methods Male C57BL/6J mice were stratified by body weight and randomly divided into control group, model group, fluoxetine hydrochloride (10 mg/kg) group and CDB volatile oil high-and low-dose (73.6, 36.8 mg/kg) groups. Mice in each group were gavaged 16 consecutive days, and the model was established by intraperitoneal injection of 1 mg/kg LPS (20 mL/kg) on 13th to 15th day of administration. Depression-like behavior was observed by sucrose preference test, forced swimming test and tail suspension test. Levels of interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) in serum were measured by ELISA; Levels of malondialdehyde (MDA), glutathione (GSH) and superoxide dismutase (SOD) activity in hippocampus of mice were measured by chemically; The number of mouse hippocampal Nissl bodies was detected by Nissen staining; Immunofluorescence method was used to detect the expression of ionized calcium-binding adapter molecule-1 (Iba-1) in CA3 area of mouse hippocampus; Western blotting was used to detect brain-derived neurotrophic factor (BDNF), p-PI3K/PI3K, p-Akt/Akt, Nrf2, heme oxygenase-1 (HO-1), SOD1, p-p65/p65, IL-1β and Iba-1 protein expressions in hippocampus. Results CDB volatile oil significantly increased the rate of sucrose preference in model mice (P < 0.01), shortened the immobility time of forced swimming and tail suspension test (P < 0.05, 0.01), significantly decreased the hippocampal MDA level (P < 0.05), increased GSH level and SOD activity (P < 0.05), decreased the levels of IL-1β and TNF-α in serum (P < 0.01), significantly increased the average fluorescence intensity of Nissl bodies in hippocampal CA3 region of mice and inhibited the expression of Iba-1 in CA3 region (P < 0.05, 0.01), significantly increased BDNF, p-PI3K/PI3K, p-Akt/Akt, Nrf2, HO-1 and SOD1 expressions in hippocampus (P < 0.05, 0.01), inhibited p-p65/p65, IL-1β and Iba-1 protein expressions (P < 0.05, 0.01). Conclusion CDB volatile oil increases antioxidant level and reduces neuroinflammation by activating PI3K/Akt/Nrf2 signaling pathway, and thus exerting antidepressant effects.

成都中医药大学西南特色中药资源国家重点实验室开放基金项目（2020XSGG002）；成都中医药大学杏林学者项目（QJJJ2022012）