目的 基于血清代謝組學(xué)探討白鮮皮酒炙前后對(duì)銀屑病的作用，揭示酒炙白鮮皮的增效機(jī)制。方法 采用背部涂抹咪喹莫特乳膏的方法建立銀屑病模型，小鼠隨機(jī)分為對(duì)照組、模型組、甲氨蝶呤（1 mg/kg）組及白鮮皮高、中、低劑量（5.2、2.6、1.3 g/kg）組和酒炙白鮮皮高、中、低劑量（5.2、2.6、1.3 g/kg）組，每組8只，造模同時(shí)給藥7 d。采用蘇木素-伊紅（hematoxylin-eosin，HE）染色觀察皮損組織的病理變化；ELISA檢測(cè)血清中白細(xì)胞介素-17（interleukin-17，IL-17）、IL-23、腫瘤壞死因子-α（tumor necrosis factor-α，TNF-α）的水平；Western blotting和qRT-PCR檢測(cè)皮損組織中TNF-α、IL-17、IL-23、IL-22、IL-1β蛋白和mRNA的表達(dá)水平；采用超高效液相色譜法-串聯(lián)四極桿飛行時(shí)間質(zhì)譜（UPLC-Q-TOF-MS）檢測(cè)小鼠血清中非靶向代謝物，篩選潛在生物標(biāo)志物，并結(jié)合HMDB數(shù)據(jù)庫(kù)和京都基因與基因組百科全書（Kyoto encyclopedia of genes and genomes，KEGG）數(shù)據(jù)庫(kù)分析潛在的代謝通路。結(jié)果 生品白鮮皮和酒炙白鮮皮均能緩解咪喹莫特誘導(dǎo)的銀屑病小鼠癥狀，改善皮損組織病理?yè)p傷，減輕皮損組織炎癥因子的蛋白和mRNA表達(dá)水平（P＜0.05、0.01、0.001）。與生品白鮮皮相比，酒炙白鮮皮對(duì)銀屑病小鼠的改善作用更為顯著。酒炙白鮮皮組篩選出32個(gè)差異代謝物，主要與花生四烯酸代謝、視黃醇代謝、甘油磷脂代謝和苯丙氨酸代謝等通路有關(guān)；白鮮皮組篩選出24個(gè)差異代謝物，主要與花生四烯酸代謝、視黃醇代謝和鞘脂代謝等通路有關(guān)。甘油磷脂代謝和苯丙氨酸代謝為白鮮皮酒炙后抗銀屑病增效的通路。結(jié)論 白鮮皮經(jīng)酒炙后，可能通過(guò)抑制炎癥反應(yīng)，干預(yù)甘油磷脂代謝和苯丙氨酸代謝通路，發(fā)揮更強(qiáng)的改善銀屑病的作用。

Objective To explore the effects of Baixianpi (Dictamni Cortex) before and after wine processing on psoriasis based on serum metabolomics, and reveal the enhanced efficacy mechanism of wine-processed Dictamni Cortex. Methods A psoriasis model was established by topically applying imiquimod cream to the back of mice. The mice were randomly divided into control group, model group, methotrexate (1 mg/kg) group, Dictamni Cortex high-, medium-, low-dose (5.2, 2.6, 1.3 g/kg) groups and wine-processed Dictamni Cortex high-, medium-, low-dose (5.2, 2.6, 1.3 g/kg) groups, with eight mice in each group. The mice were administered drugs by gavage while modeling for 7 d. Hematoxylin-eosin (HE) staining was used to observe the pathological changes in skin lesion tissues. The levels of interleukin-17 (IL-17), IL-23 and tumor necrosis factor-α (TNF-α) in serum were detected by ELISA. Western blotting and qRT-PCR were used to detect the protein and mRNA expression levels of TNF-α, IL-17, IL-23, IL-22 and IL-1β in skin lesion tissues. Ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS) was used to detect non-targeted metabolites in serum of mice, potential biomarkers were screened, and potential metabolic pathways were analyzed by combining HMDB database and Kyoto encyclopedia of genes and genomes (KEGG) database. Results Both raw and wine-processed Dictamni Cortex could alleviate the symptoms of psoriasis mice induced by imiquimod, improve pathological damage to skin lesions, and reduce protein and mRNA expression levels of inflammatory factors in skin lesions (P < 0.05, 0.01, 0.001). Compared with raw Dictamni Cortex, wine-processed Dictamni Cortex had a more significant improvement effect on psoriasis mice. A total of 32 differential metabolites were screened from wine-processed Dictamni Cortex group, mainly related to pathways such as arachidonic acid metabolism, retinol metabolism, glycerophospholipid metabolism and phenylalanine metabolism; A total of 24 differential metabolites were screened from Dictamni Cortex group, mainly related to pathways such as arachidonic acid metabolism, retinol metabolism and sphingolipid metabolism. Glycerophospholipid metabolism and phenylalanine metabolism were pathways that enhance the anti-psoriasis effect of wine-processed Dictamni Cortex. Conclusion After wine-processed, Dictamni Cortex may play a stronger role in improving psoriasis by inhibiting inflammatory response and interfering with glycerophospholipid metabolism and phenylalanine metabolism pathways.

R285.5

國(guó)家重點(diǎn)研發(fā)計(jì)劃-中醫(yī)藥現(xiàn)代化（2022YFC3502100）；國(guó)家重點(diǎn)研發(fā)計(jì)劃-中醫(yī)藥現(xiàn)代化（2022YFC3502102）；國(guó)家重點(diǎn)研發(fā)計(jì)劃-中醫(yī)藥現(xiàn)代化（2022YFC3502102-04）