目的 探究丹参白疕消方联合甲氨蝶呤治疗银屑病的作用机制。方法 将BALB/c小鼠随机分为对照组、模型组、雷公藤多苷（12 mg/kg）组、甲氨蝶呤（1 mg/kg）组及丹参白疕消方低、高剂量（6、12 g/kg）组和低剂量丹参白疕消方＋甲氨蝶呤组、高剂量丹参白疕消方＋甲氨蝶呤组，每组6只。小鼠连续14 d于背部涂抹5%咪喹莫特乳膏造模，第8～14天给予相应药物干预。通过银屑病面积和严重程度指数（psoriasis area and severity index，PASI）评分、肝脏/脾脏指数、皮损组织病理染色、血清炎症因子水平以及皮损组织丝裂原活化蛋白激酶（mitogen-activated protein kinase，MAPK）/核因子-κB（nuclear factor-κB，NF-κB）通路相关蛋白表达，综合评价各组疗效，探究丹参白疕消方联合甲氨蝶呤治疗银屑病的作用机制。结果 与模型组比较，各给药组可显著降低PASI评分、表皮厚度（P＜0.01），显著抑制血清中白细胞介素-6（interleukin-6，IL-6）、IL-17A水平及皮损组织p38、细胞外信号调节激酶1/2（extracellular regulated kinase 1/2，ERK1/2）、NF-κB p65、核因子-κBα抑制蛋白（inhibitor of nuclear factor-κBα，IκBα）的磷酸化水平（P＜0.05、0.01）。与甲氨蝶呤组比较，低剂量丹参白疕消方＋甲氨蝶呤组可显著降低肝脏和脾脏指数（P＜0.01），显著抑制血清中肿瘤坏死因子-α（tumor necrosis factor-α，TNF-α）、IL-23水平以及皮损组织p38的磷酸化水平（P＜0.05、0.01）；高剂量丹参白疕消方＋甲氨蝶呤组可显著抑制血清中IL-23水平以及皮损组织c-Jun氨基末端激酶（c-Jun N-terminal kinase，JNK）、NF-κB p65的磷酸化水平（P＜0.05、0.01）。主成分分析结果显示联和用药组与对照组最接近，药效最好。结论 丹参白疕消方与甲氨蝶呤联用能够减轻咪喹莫特诱导的银屑病小鼠症状，其作用机制可能与抑制MAPK/NF-κB通路有关。

Objective To investigate the mechanism of Danshen Baibixiao Formula (丹参白疕消方, DBF) combined with methotrexate (MTX) in the treatment of psoriasis. Methods BALB/c mice were randomly divided into control group, model group, Tripterygium wilfordii polyglycoside (12 mg/kg) group, MTX (1 mg/kg) group, DBF low- and high-dose (6, 12 g/kg) groups, low- and high-dose groups of DBF combined with MTX, with six mice in each group. Mice were treated with 5% imiquimod cream on their backs for 14 consecutive days to create a model, and corresponding drug intervention was administered from day 8 to day 14. Through the evaluation of psoriasis area and severity index (PASI) score, liver/spleen index, pathological staining of skin lesions, serum inflammatory factor levels, and protein expressions related to the mitogen activated protein kinase (MAPK)/nuclear factor-κB (NF-κB) pathway in skin lesions, the efficacy of each group was comprehensively evaluated to explore the mechanism of DBF combined with methotrexate in the treatment of psoriasis.Results Compared with model group, each administration group could significantly reduce the PASI score and epidermal thickness (P < 0.01), significantly inhibit the levels of interleukin-6 (IL-6), IL-17A in serum and phosphorylation of p38, extracellular regulated kinase 1/2 (ERK1/2), NF-κB p65, inhibitor of nuclear factor-κBα (IκBα) in skin lesions (P < 0.05, 0.01). Compared with MTX, low-dose combination group could significantly reduce the liver and spleen indexes (P < 0.01), significantly inhibit the levels of tumor necrosis factor-α (TNF-α), IL-23 in serum and phosphorylation of p38 in skin lesions (P < 0.05, 0.01); High-dose combination group could significantly inhibit the level of IL-23 in serum and phosphorylation of c-Jun N-terminal kinase (JNK), NF-κB p65 in skin lesions (P < 0.05, 0.01). The results of principal component analysis showed that the combination group was closest to the control group and had the best efficacy. Conclusion The combination of DBF and MTX can alleviate the symptoms of psoriasis mice induced by imiquimod, and and its mechanism may be associated with the inhibition of MAPK/NF-κB pathway.

R285.5

武汉市中医药科研项目重大项目（WZ22M02）