目的 应用血清代谢组学技术探讨白鲜皮水提物（ DDAE）治疗银屑病的潜在机制。方法 将50只大鼠随机分为对照组、模型组、克银丸（阳性药，0.9 g·kg^-1）组和DDAE高、低剂量（ 2.7、0.8 g·kg^-1）组，采用5%盐酸普萘洛尔乳膏剂外涂构建大鼠银屑病模型，每天ig给药1次，连续14 d。苏木精-伊红（ HE）染色观察大鼠皮肤组织病理变化并进行Baker评分；免疫组化法检测大鼠皮肤组织增殖细胞核抗原（ PCNA）和细胞角蛋白（ CK-17）表达水平；实时荧光定量PCR（ qRTPCR）法检测大鼠皮损组织中的炎症因子白细胞介素（ IL）-1β、IL-17A、IL-22、IL-23A和肿瘤坏死因子（ TNF）-α mRNA表达水平；同时对大鼠血清进行代谢组学分析，筛选差异代谢物并进行通路富集分析。结果 与对照组比较，模型组皮肤组织出现角质层增生，表皮增厚，角化不全或角化过度等现象；克银丸组和DDAE高、低剂量组皮肤组织有少量的角质层增生，表皮轻度变薄，较模型组病理变化明显减轻。与对照组比较，模型组的Baker病理评分升高（ P＜0.001），PCNA、CK-17蛋白和IL-1β、IL-17A、IL-22、IL-23A和TNF-α mRNA表达明显升高（ P＜0.001）；与模型组比较，克银丸组和DDAE高、低剂量组的Baker病理评分显著下降（ P＜0.05、0.01、0.001），PCNA、CK-17蛋白和IL-1β、IL-17A、IL-22、IL-23A和TNF-α mRNA表达明显下降（ P＜0.05、0.01、0.001）。通过血清代谢组学发现，对照组与模型组血清中存在35个差异代谢物，主要与4条代谢通路有关，模型组与DDAE高剂量组血清中存在77个差异代谢物，主要与5条代谢通路有关，其中共同的代谢通路为花生四烯酸代谢通路、乙醛酸和二羧酸代谢通路，涉及主要代谢物有花生四烯酸和乙醛酸。结论 白鲜皮对银屑病具有治疗作用，可能通过调节花生四烯酸代谢、乙醛酸和二羧酸代谢来抑制银屑病的发生。

Objective To explore the potential mechanism of aqueous extract from Dictamnus dasycarpus (DDAE) in the treatment of psoriasis by using serum metabolomics technology. Methods Fifty rats were randomly divided into control group, model group, Kegyin Pill (positive drug, 0.9 g·kg^-1) group, and DDAE high and low dose (2.7, 0.8 g·kg^-1) groups. A psoriasis model was established by applying 5% propranolol hydrochloride cream externally. The rats were administered ig once a day for 14 d. HE staining was used to observe the pathological changes of rat skin tissue and perform Baker scoring. Immunohistochemistry was used to detect the expression levels of proliferating cell nuclear antigen (PCNA) and cytokeratin (CK-17) in rat skin tissue. Real-time fluorescence quantitative PCR (qRT-PCR) was used to detect the mRNA expression levels of inflammatory factors interleukin (IL)-1β, IL-17A, IL- 22, IL-23A and tumor necrosis factor (TNF)-α in rat skin lesions. Meanwhile, serum metabolomics analysis was conducted on the rats to screen for differential metabolites and perform pathway enrichment analysis. Results Compared with the control group, the model group showed hyperkeratosis, epidermal thickening, parakeratosis or hyperkeratosis in the skin tissue; Kegyin Pill group and DDAE high and low dose groups had a small amount of hyperkeratosis and mild epidermal thinning in the skin tissue, with significantly reduced pathological changes compared to the model group. Compared with the control group, the Baker pathological score of the model group increased (P < 0.001), and the expression of PCNA, CK-17 protein and IL-1β, IL-17A, IL-22, IL-23A and TNF-α mRNA significantly increased (P < 0.001). Compared with the model group, the Baker pathological scores of the Kegyin Pill group and the high and low dose DDAE groups significantly decreased (P < 0.05, 0.01, 0.001), and the expression of PCNA, CK-17 protein and IL- 1β, IL-17A, IL-22, IL-23A and TNF-α mRNA significantly decreased (P < 0.05, 0.01, 0.001). Through serum metabolomics, it was found that there were 35 differential metabolites in the serum of the control group and the model group, mainly related to four metabolic pathways; there were 77 differential metabolites in the serum of the model group and the high dose DDAE group, mainly related to five metabolic pathways. The common metabolic pathways were arachidonic acid metabolism and glyoxylic acid and dicarboxylic acid metabolism, involving the main metabolites arachidonic acid and glyoxylic acid. Conclusion DDAE has a therapeutic effect on psoriasis and may inhibit the occurrence of psoriasis by regulating arachidonic acid metabolism and glyoxylic acid and dicarboxylic acid metabolism.

R285.5

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