目的 基于血清代谢组学探讨白鲜皮酒炙前后对银屑病的作用，揭示酒炙白鲜皮的增效机制。方法 采用背部涂抹咪喹莫特乳膏的方法建立银屑病模型，小鼠随机分为对照组、模型组、甲氨蝶呤（1 mg/kg）组及白鲜皮高、中、低剂量（5.2、2.6、1.3 g/kg）组和酒炙白鲜皮高、中、低剂量（5.2、2.6、1.3 g/kg）组，每组8只，造模同时给药7 d。采用苏木素-伊红（hematoxylin-eosin，HE）染色观察皮损组织的病理变化；ELISA检测血清中白细胞介素-17（interleukin-17，IL-17）、IL-23、肿瘤坏死因子-α（tumor necrosis factor-α，TNF-α）的水平；Western blotting和qRT-PCR检测皮损组织中TNF-α、IL-17、IL-23、IL-22、IL-1β蛋白和mRNA的表达水平；采用超高效液相色谱法-串联四极杆飞行时间质谱（UPLC-Q-TOF-MS）检测小鼠血清中非靶向代谢物，筛选潜在生物标志物，并结合HMDB数据库和京都基因与基因组百科全书（Kyoto encyclopedia of genes and genomes，KEGG）数据库分析潜在的代谢通路。结果 生品白鲜皮和酒炙白鲜皮均能缓解咪喹莫特诱导的银屑病小鼠症状，改善皮损组织病理损伤，减轻皮损组织炎症因子的蛋白和mRNA表达水平（P＜0.05、0.01、0.001）。与生品白鲜皮相比，酒炙白鲜皮对银屑病小鼠的改善作用更为显著。酒炙白鲜皮组筛选出32个差异代谢物，主要与花生四烯酸代谢、视黄醇代谢、甘油磷脂代谢和苯丙氨酸代谢等通路有关；白鲜皮组筛选出24个差异代谢物，主要与花生四烯酸代谢、视黄醇代谢和鞘脂代谢等通路有关。甘油磷脂代谢和苯丙氨酸代谢为白鲜皮酒炙后抗银屑病增效的通路。结论 白鲜皮经酒炙后，可能通过抑制炎症反应，干预甘油磷脂代谢和苯丙氨酸代谢通路，发挥更强的改善银屑病的作用。

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

国家重点研发计划-中医药现代化（2022YFC3502100）；国家重点研发计划-中医药现代化（2022YFC3502102）；国家重点研发计划-中医药现代化（2022YFC3502102-04）