目的 研究柴胡Bupleuri Radix不同极性部位对慢性不可预知应激（chronic unpredictable mild stress，CUMS）模型大鼠抑郁样行为干预作用和神经递质调节作用，筛选出最佳药效部位，并建立一种能够测定抑郁大鼠胆汁酸谱的方法。方法 雄性SD大鼠随机分为对照组、模型组、盐酸文拉法辛（35 mg/kg）组、柴胡低极性部位（15 g/kg）组、柴胡中极性部位（15 g/kg）和柴胡高极性部位（15 g/kg）组，每组9只，造模28 d同时给药，动态测定大鼠的体质量变化，通过糖水偏好实验和旷场实验检测行为学变化；采用UPLC-MS测定血清中色氨酸（tryptophane，Trp）、5-羟色胺（5-hydroxytryptamine，5-HT）、5-羟基吲哚乙酸（5-hydroxyindoleacetic acid，5-HIAA）、去甲肾上腺素（noradrenaline，NE）、多巴胺（dopamine，DA）、乙酰胆碱（acetylcholine，Ach）、γ-氨基丁酸（γ-aminobutyricacid，GABA）、谷氨酸（glutamic acid，Glu）、酪氨酸（tyrosine，Tyr）含量；采用全自动生化分析仪测定γ-谷氨酰转肽酶（γ-glutamyl transpeptidase，γ-GT）、碱性磷酸酶（alkaline phosphatase，ALP）活性和血清总胆红素（serum bilirubin，TBIL）含量；采用ELISA测定盲肠内容物中总胆汁酸（total bile acid，TBA）水平；采用UPLC-MS/MS拟靶向代谢组学建立36种胆汁酸的拟靶向相对定量方法，测定盲肠内容物胆汁酸谱，并对组间胆汁酸差异性进行分析。结果 柴胡不同极性部位组和盐酸文拉法辛组均可回调CUMS引起的大鼠体质量、糖水偏爱率、直立次数、水平穿越格数异常和血清中Trp、5-HT、5-HIAA、NE、DA、Ach、GABA、Glu、Tyr水平（P＜0.05、0.01、0.001），且柴胡低极性部位回调效果最好。同时柴胡低极性部位可显著回调大鼠血清γ-GT活性及血清TBIL、盲肠内容物TBA含量（P＜0.05、0.01）；建立了36种胆汁酸的拟靶向相对定量方法，所建立的方法具有良好的稳定性，胆汁酸谱分析表明，柴胡低极性部位可调节盲肠内容物胆汁酸谱，通过回调其中5种差异胆汁酸（牛磺熊去氧胆酸、熊去氧胆酸、牛磺去氧胆酸、牛磺鹅去氧胆酸、牛磺石胆酸）发挥药效作用。结论 柴胡低极性部位为抗抑郁最佳药效部位，同时能够调节胆汁酸谱的代谢紊乱，发挥肝保护作用。

Objective To study the intervention effect of different polar parts of Chaihu (Bupleuri Radix) on depression-like behavior and neurotransmitter regulation in chronic unpredictable animal stress model (CUMS) rats, screen out the best effective parts, and establish a method to determine the bile acid spectrum of depressed rats. Methods Male SD rats were randomly divided into control group, model group, venlafaxine hydrochloride (35 mg/kg) group, Bupleuri Radix low polarity fraction (15 g/kg) group, medium polarity fraction (15 g/kg) group and high polarity fraction (15g/kg) group, with nine rats in each group. 28 d of modeling and administration simultaneously, the body weight changes of rats were dynamically measured, and the behavioral changes were detected by sucrose preference test and open field test. UPLC-MS was used to determine the contents of tryptophane (Trp), 5-hydroxytryptamine (5-HT), 5-hydroxyindoleacetic acid (5-HIAA), noradrenaline (NE), dopamine (DA), acetylcholine (Ach), γ-aminobutyric acid (GABA), glutamic acid (Glu) and tyrosine (Tyr) in serum. The activities of γ-glutamyl transpeptidase (γ-GT), alkaline phosphatase (ALP) and serum total bilirubin (TBIL) were measured by automatic biochemical analyzer. The level of total bile acid (TBA) in cecal contents was determined by ELISA. UPLC-MS/MS quasi-targeted metabolomics was used to establish a quasi-targeted relative quantitative method for 36 bile acids, and the bile acid spectrum of cecal contents was determined, and the differences of bile acids between groups were analyzed. Results The body weight, sugar water preference rate, rearing times, horizontal crossing grid abnormalities and serum levels of Trp, 5-HT, 5-HIAA, NE, DA, Ach, GABA, Glu and Tyr caused by CUMS could be callbacked by different polar parts of Bupleuri Radix and venlafaxine hydrochloride group (P < 0.05, 0.01, 0.001), and the callback effect of low polar parts of Bupleuri Radix was the best. At the same time, the low-polarity fraction of Bupleuri Radix can significantly restore the serum γ-GT activity and serum TBIL, cecal content TBA content (P < 0.05, 0.01); A quasi-targeted relative quantitative method for 36 bile acids was established, and the established method had good stability. The bile acid spectrum analysis showed that the low-polar part of Bupleuri Radix could adjust the bile acid spectrum of cecal contents. Bupleuri Radix could play a pharmacodynamic role by restoring five kinds of differential bile acids (tauroursodeoxycholic acid, ursodeoxycholic acid, tauroursodeoxycholic acid, taurochenodeoxycholic acid, taurocholic acid). Conclusion The low polarity fraction of Bupleuri Radix is the best pharmacodynamic site for antidepressant, and it can regulate the metabolic disorder of bile acid spectrum and play a role in liver protection.

国家自然科学基金面上项目（82174099）；山西省基础应用项目面上项目（20210302123432）；名优晋药再开发山西省重点实验室（202104010910001）；地产中药功效物质研究与利用山西省重点实验室（201605D111004）