目的 探討四妙勇安湯對尿酸鈉誘導的痛風性關節(jié)炎大鼠的作用機制。方法 運用網(wǎng)絡藥理學方法預測四妙勇安湯干預痛風性關節(jié)炎的靶點，構(gòu)建“成分-靶點-通路”關系網(wǎng)絡。將 48 只雄性 SD 大鼠隨機分為對照組、模型組、秋水仙堿（陽性對照，0.000 3 g·kg^-1）組及四妙勇安湯低、中、高劑量（6.075、12.150、24.300 g·kg^-1）組，每組 8只，預防性 ig給藥，每天1次，持續(xù)7 d，ig第3天，除了對照組，構(gòu)建痛風性關節(jié)炎大鼠模型。測量并計算大鼠踝關節(jié)腫脹度，HE染色檢測大鼠踝關節(jié)滑膜組織病理學改變；ELISA試劑盒法檢測各組大鼠血清中炎癥因子白細胞介素（IL）-17A、IL-17F、環(huán)氧化酶-2 （COX-2）、趨化因子配體 2 （CXCL2）、IL-1β、腫瘤壞死因子- α （TNF） - α 的水平；采用實時熒光定量PCR（qRT-PCR）和Western blotting檢測關節(jié)組織中MEK1/2-ErK1/2途徑基因mRNA和蛋白表達水平。結(jié)果 網(wǎng)絡藥理學結(jié)果顯示，AKT1、ALB、TNF、HSP90AA1、EGFR、SRC、VEGFA、CCND1、HRAS、MAPK3、MAP2K1可能是四妙勇安湯治療痛風性關節(jié)炎的關鍵靶點；β-谷甾醇、山柰酚、槲皮素、木犀草素可能為治療痛風性關節(jié)炎中較重要的有效成分；生物過程（BP）中富集基因主要與炎癥反應、對細胞遷移的積極調(diào)節(jié)、對外部刺激反應的負調(diào)節(jié)、小分子代謝過程的調(diào)控等過程密切相關，細胞組分（CC）分析包括分泌顆粒、細胞質(zhì)囊泡、內(nèi)質(zhì)網(wǎng)、高爾基、血小板顆粒等，分子功能（MF）中富集基因靠前的有轉(zhuǎn)錄因子結(jié)合、蛋白激酶活性、激酶調(diào)節(jié)活性等；KEGG代謝通路主要富集于MAPK信號通路、PI3K-Akt信號通路、IL-17信號通路、Ras信號通路等。與模型組比較，四妙勇安湯高劑量可明顯改善踝關節(jié)腫脹度（P＜0.05）；中、高劑量可緩解痛風性關節(jié)炎大鼠滑膜組織炎性浸潤；中、高劑量組炎癥因子水平顯著降低（P＜0.05、0.01）；中、高劑量組MAPK3、MAP2K1的基因mRNA表達量顯著下調(diào)（P＜0.01）；高劑量組ErK1/2、MEK1/2蛋白的表達量顯著下調(diào)（P＜0.01）。結(jié)論 四妙勇安湯對痛風性關節(jié)炎大鼠具有治療作用，其可能是通過抑制MAPK信號通路關鍵靶點ErK1/2、MEK1/2的表達，抑制下游炎癥因子IL-17、TNF-α、IL-1β表達，減輕炎性反應，從而發(fā)揮對痛風性關節(jié)炎的治療作用。

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

貴州中醫(yī)藥大學大學生創(chuàng)新創(chuàng)業(yè)訓練計劃項目（貴中醫(yī)大創(chuàng)合字（2021）16號）；貴州省科學技術基金（黔科合基礎-ZK［2021］一般515）；貴州省教育廳2023年度自然科學研究項目（黔教技［2023］069號）