目的 探讨茯苓极性提取物对慢性温和不可预知性应激（CUMS）大鼠神经递质和昼夜节律代谢途径的调节作用。方法 将雄性SD大鼠随机分为对照组、CUMS模型组、阳性药盐酸文拉法辛组（35 mg/kg）、茯苓极性提取物组（15 g/kg），造模同时ig给药28 d，动态观察各组大鼠体质量、糖水偏爱率、旷场行为；采用UHPLC-MS/MS方法检测血清中色氨酸（Trp）、5-羟色胺（5-HT）、5-羟基吲哚乙酸（5-HIAA）、去甲肾上腺素（NE）、多巴胺（DA）、乙酰胆碱（Ach）、γ-氨基丁酸（GABA）、谷氨酸（Glu）、GABA/Glu的量，并应用实时荧光定量PCR（qRT-PCR）技术检测肝组织中与昼夜节律通路相关的10种基因表达水平的变化。结果 茯苓极性提取物可显著回调CUMS引起的糖水偏爱率、直立次数、水平穿越格数、理毛时间的异常，且可回调血清中5-HT、5-HIAA、Trp、NE、Ach、GABA、GABA/Glu水平，调节肝脏中Arntl、Per1、Per2、Per3、Nr1d1的基因表达水平。结论 茯苓极性提取物可增强5-HT代谢途径，调节Ach-NE信号的相互作用以及氨基酸神经递质比例的平衡，回调参与昼夜节律的Arntl、Per1、Per2、Per3、Nr1d1的表达水平改善CUMS大鼠神经递质及昼夜节律紊乱。

Objective To explore the regulation of polar extract of Poria cocos on neurotransmitter and circadian rhythm metabolic pathway. Methods Male SD rats were randomly divided into blank group, chronic unpredictable mild stress (CUMS) model group, positive drug venlafaxine hydrochloride group (35 mg/kg), and polar extract of P. cocos group (15 g/kg). Rats were modeled and ig administrated for 28 d simultaneously, and the body weight, sugar preference rate, and opening behavior were observed dynamically after administration. The levels of tryptophan (Trp), 5-hydroxytryptophan (5-HT), and 5-hydroxyindole acetic acid (5-HIAA), noradrenaline (NE), dopamine (DA), acetylcholiner (Ach), γ-aminobutyric acid (GABA), glutamic acid (Glu), the proportion of GABA/Glu in serum were measured by LC-MS. The expression of key genes in the circadian rhythm pathway in liver tissue was detected by using qRT-PCR. Results Polar extracts of P. cocos significantly improved the abnormality of the sugar preference rate and opening behavior. And polar extracts of P. cocos significantly restored the levels of 5-HT, 5-HIAA, Trp, NE, Ach, GABA, the proportion of GABA/Glu in serum and regulated the gene expression levels of Arntl, Per1, Per2, Per3, and Nr1d1 in hepatocyte. Conclusion The polar extract of P. cocos could improve neurotransmitters and circadian rhythm disorders in CUMS rats through enhancing the 5-HT metabolic pathway, regulating Ach-NE signaling interaction and the equilibrium of proportion of amino acids neurotransmitter and restoring the expression levels of Arntl, Per1, Per2, Per3, and Nr1d1 involved in the circadian rhythm.

国家自然科学基金资助项目（81473415）；山西省重点研发计划（社会发展方面）项目（201803D31019）；山西省应用基础研究优秀青年基金项目（201701D211009）；山西省科技创新重点团队（201605D131045-18）；地产中药功效物质研究与利用山西省重点实验室项目（201705D111008-21）