目的 應(yīng)用血清代謝組學(xué)技術(shù)探討白鮮皮水提物（ DDAE）治療銀屑病的潛在機(jī)制。方法 將50只大鼠隨機(jī)分為對照組、模型組、克銀丸（陽性藥，0.9 g·kg^-1）組和DDAE高、低劑量（ 2.7、0.8 g·kg^-1）組，采用5%鹽酸普萘洛爾乳膏劑外涂構(gòu)建大鼠銀屑病模型，每天ig給藥1次，連續(xù)14 d。蘇木精-伊紅（ HE）染色觀察大鼠皮膚組織病理變化并進(jìn)行Baker評分；免疫組化法檢測大鼠皮膚組織增殖細(xì)胞核抗原（ PCNA）和細(xì)胞角蛋白（ CK-17）表達(dá)水平；實(shí)時熒光定量PCR（ qRTPCR）法檢測大鼠皮損組織中的炎癥因子白細(xì)胞介素（ IL）-1β、IL-17A、IL-22、IL-23A和腫瘤壞死因子（ TNF）-α mRNA表達(dá)水平；同時對大鼠血清進(jìn)行代謝組學(xué)分析，篩選差異代謝物并進(jìn)行通路富集分析。結(jié)果 與對照組比較，模型組皮膚組織出現(xiàn)角質(zhì)層增生，表皮增厚，角化不全或角化過度等現(xiàn)象；克銀丸組和DDAE高、低劑量組皮膚組織有少量的角質(zhì)層增生，表皮輕度變薄，較模型組病理變化明顯減輕。與對照組比較，模型組的Baker病理評分升高（ P＜0.001），PCNA、CK-17蛋白和IL-1β、IL-17A、IL-22、IL-23A和TNF-α mRNA表達(dá)明顯升高（ P＜0.001）；與模型組比較，克銀丸組和DDAE高、低劑量組的Baker病理評分顯著下降（ 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表達(dá)明顯下降（ P＜0.05、0.01、0.001）。通過血清代謝組學(xué)發(fā)現(xiàn)，對照組與模型組血清中存在35個差異代謝物，主要與4條代謝通路有關(guān)，模型組與DDAE高劑量組血清中存在77個差異代謝物，主要與5條代謝通路有關(guān)，其中共同的代謝通路為花生四烯酸代謝通路、乙醛酸和二羧酸代謝通路，涉及主要代謝物有花生四烯酸和乙醛酸。結(jié)論 白鮮皮對銀屑病具有治療作用，可能通過調(diào)節(jié)花生四烯酸代謝、乙醛酸和二羧酸代謝來抑制銀屑病的發(fā)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

國家重點(diǎn)研發(fā)計劃—中醫(yī)藥現(xiàn)代化（2022YFC3502100，2022YFC3502102，2022YFC3502102-04）