目的 探讨四妙勇安汤对尿酸钠诱导的痛风性关节炎大鼠的作用机制。方法 运用网络药理学方法预测四妙勇安汤干预痛风性关节炎的靶点，构建“成分-靶点-通路”关系网络。将 48 只雄性 SD 大鼠随机分为对照组、模型组、秋水仙碱（阳性对照，0.000 3 g·kg^-1）组及四妙勇安汤低、中、高剂量（6.075、12.150、24.300 g·kg^-1）组，每组 8只，预防性 ig给药，每天1次，持续7 d，ig第3天，除了对照组，构建痛风性关节炎大鼠模型。测量并计算大鼠踝关节肿胀度，HE染色检测大鼠踝关节滑膜组织病理学改变；ELISA试剂盒法检测各组大鼠血清中炎症因子白细胞介素（IL）-17A、IL-17F、环氧化酶-2 （COX-2）、趋化因子配体 2 （CXCL2）、IL-1β、肿瘤坏死因子- α （TNF） - α 的水平；采用实时荧光定量PCR（qRT-PCR）和Western blotting检测关节组织中MEK1/2-ErK1/2途径基因mRNA和蛋白表达水平。结果 网络药理学结果显示，AKT1、ALB、TNF、HSP90AA1、EGFR、SRC、VEGFA、CCND1、HRAS、MAPK3、MAP2K1可能是四妙勇安汤治疗痛风性关节炎的关键靶点；β-谷甾醇、山柰酚、槲皮素、木犀草素可能为治疗痛风性关节炎中较重要的有效成分；生物过程（BP）中富集基因主要与炎症反应、对细胞迁移的积极调节、对外部刺激反应的负调节、小分子代谢过程的调控等过程密切相关，细胞组分（CC）分析包括分泌颗粒、细胞质囊泡、内质网、高尔基、血小板颗粒等，分子功能（MF）中富集基因靠前的有转录因子结合、蛋白激酶活性、激酶调节活性等；KEGG代谢通路主要富集于MAPK信号通路、PI3K-Akt信号通路、IL-17信号通路、Ras信号通路等。与模型组比较，四妙勇安汤高剂量可明显改善踝关节肿胀度（P＜0.05）；中、高剂量可缓解痛风性关节炎大鼠滑膜组织炎性浸润；中、高剂量组炎症因子水平显著降低（P＜0.05、0.01）；中、高剂量组MAPK3、MAP2K1的基因mRNA表达量显著下调（P＜0.01）；高剂量组ErK1/2、MEK1/2蛋白的表达量显著下调（P＜0.01）。结论 四妙勇安汤对痛风性关节炎大鼠具有治疗作用，其可能是通过抑制MAPK信号通路关键靶点ErK1/2、MEK1/2的表达，抑制下游炎症因子IL-17、TNF-α、IL-1β表达，减轻炎性反应，从而发挥对痛风性关节炎的治疗作用。

Objective To investigate the effect of Simiao Yong'an Decoction on gouty arthritis rats induced by monosodium urate (MUS) and its possible mechanism.Methods The target of Simiao Yong'an Decoction in the intervention of gouty arthritis was predicted by network pharmacology, and the relationship network of active ingredient-target and target-pathway was constructed. Totally 48 male SD rats were randomly divided into control group, model group, Simiao Yong'an Decoction low, medium and high dose group (6.075, 12.150, and 24.300 g·kg^-1), with eight rats in each group. Prophylactic ig administration once a day for seven days. On the 3rd day of ig administration, except for the control group, the GA rat model was established according to the classical modeling method. The different doses of Simiao Yong'an Decoction were injected into the stomach to measure and calculate the degree of ankle swelling, and the histopathological changes of ankle synovium and the levels of inflammatory factors in serum of rats in each group were detected. Finally, real-time quantitative fluorescent PCR (qRT-PCR) and Western blotting were used to detect the mRNA and protein expression levels of MEK1/2-ErK1/2 pathway genes in joint tissues.Results The network pharmacology results show that AKT1, ALB, TNF, HSP90AA1, EGFR, SRC, VEGFA, CCND1, and HRAS may be the key targets of Simiao Yong'an Decoction for the treatment of gouty arthritis; β -sitosterol, kaempferol, quercetin, and lutein may be the more important effective components for the treatment of gouty arthritis; the enriched genes in biological processes (BP) are mainly related to inflammatory responses, positive regulation of cell migration, negative regulation of responses to external stimuli, and regulation of small molecule metabolic processes; the enriched genes in cellular components (CC) include secretory granules, cytoplasmic vesicles, endoplasmic reticulum, Golgi, and platelet granules; the enriched genes in molecular functions (MF) include transcription factor binding, protein kinase activity, and kinase regulatory activity at the front; the KEGG metabolic pathways are mainly enriched in MAPK signaling pathway, PI3K-Akt signaling pathway, IL-17 signaling pathway, and Ras signaling pathway. Compared with the model group, Simiao Yong'an Decoction at high dose can significantly improve the degree of ankle edema (P < 0.05); at medium and high doses, it can alleviate the inflammatory infiltration of synovial tissue in rats with gouty arthritis; at medium and high doses, the levels of inflammatory factors are significantly lower (P < 0.05, 0.01); at medium and high doses, the gene mRNA expression of MAPK3 and MAP2K1 is significantly downregulated (P < 0.01); at high dose, the expression of ErK1/2 and MEK1/2 proteins is significantly downregulated (P < 0.01).Conclusion Simiao Yong'an Decoction has a certain intervention effect on GA rats, and its active components may inhibit the expression of inflammatory factors such as TNF-α and IL-1β by inhibiting the expression of key targets in MAPK signaling pathway, and alleviate the inflammatory response, so as to play a therapeutic role in gouty arthritis.

R285.5

贵州中医药大学大学生创新创业训练计划项目（贵中医大创合字（2021）16号）；贵州省科学技术基金（黔科合基础-ZK［2021］一般515）；贵州省教育厅2023年度自然科学研究项目（黔教技［2023］069号）