目的 探討茯苓極性提取物對(duì)慢性溫和不可預(yù)知性應(yīng)激（CUMS）大鼠神經(jīng)遞質(zhì)和晝夜節(jié)律代謝途徑的調(diào)節(jié)作用。方法 將雄性SD大鼠隨機(jī)分為對(duì)照組、CUMS模型組、陽性藥鹽酸文拉法辛組（35 mg/kg）、茯苓極性提取物組（15 g/kg），造模同時(shí)ig給藥28 d，動(dòng)態(tài)觀察各組大鼠體質(zhì)量、糖水偏愛率、曠場(chǎng)行為；采用UHPLC-MS/MS方法檢測(cè)血清中色氨酸（Trp）、5-羥色胺（5-HT）、5-羥基吲哚乙酸（5-HIAA）、去甲腎上腺素（NE）、多巴胺（DA）、乙酰膽堿（Ach）、γ-氨基丁酸（GABA）、谷氨酸（Glu）、GABA/Glu的量，并應(yīng)用實(shí)時(shí)熒光定量PCR（qRT-PCR）技術(shù)檢測(cè)肝組織中與晝夜節(jié)律通路相關(guān)的10種基因表達(dá)水平的變化。結(jié)果 茯苓極性提取物可顯著回調(diào)CUMS引起的糖水偏愛率、直立次數(shù)、水平穿越格數(shù)、理毛時(shí)間的異常，且可回調(diào)血清中5-HT、5-HIAA、Trp、NE、Ach、GABA、GABA/Glu水平，調(diào)節(jié)肝臟中Arntl、Per1、Per2、Per3、Nr1d1的基因表達(dá)水平。結(jié)論 茯苓極性提取物可增強(qiáng)5-HT代謝途徑，調(diào)節(jié)Ach-NE信號(hào)的相互作用以及氨基酸神經(jīng)遞質(zhì)比例的平衡，回調(diào)參與晝夜節(jié)律的Arntl、Per1、Per2、Per3、Nr1d1的表達(dá)水平改善CUMS大鼠神經(jīng)遞質(zhì)及晝夜節(jié)律紊亂。

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.

國家自然科學(xué)基金資助項(xiàng)目（81473415）；山西省重點(diǎn)研發(fā)計(jì)劃（社會(huì)發(fā)展方面）項(xiàng)目（201803D31019）；山西省應(yīng)用基礎(chǔ)研究?jī)?yōu)秀青年基金項(xiàng)目（201701D211009）；山西省科技創(chuàng)新重點(diǎn)團(tuán)隊(duì)（201605D131045-18）；地產(chǎn)中藥功效物質(zhì)研究與利用山西省重點(diǎn)實(shí)驗(yàn)室項(xiàng)目（201705D111008-21）