目的 基于網(wǎng)絡(luò)藥理學(xué)探討新加白虎湯調(diào)控痛風(fēng)性關(guān)節(jié)炎的作用機(jī)制，并利用ELISA法初步驗(yàn)證其抗炎作用。方法 通過中藥系統(tǒng)藥理學(xué)分析平臺(tái)BATMAN-TCM查找新加白虎湯的化學(xué)成分及靶點(diǎn)，人類基因數(shù)據(jù)庫GeneCards查找痛風(fēng)性關(guān)節(jié)炎的相關(guān)疾病靶點(diǎn)。將新加白虎湯與痛風(fēng)性關(guān)節(jié)炎的交集靶點(diǎn)輸入STRING數(shù)據(jù)庫構(gòu)建蛋白相互作用（PPI）網(wǎng)絡(luò)，將得到的交集蛋白靶標(biāo)基因輸入Cytoscape中的ClueGo插件進(jìn)行基因本體論（GO）分析和京都基因與基因組百科全書（KEGG）通路分析。SD雄性大鼠隨機(jī)分為對(duì)照組、模型組和新加白虎湯（20 g·kg^-1）組，每天ig給藥1次，對(duì)照組和模型組ig等體積蒸餾水。除對(duì)照組外，第5天給藥后1 h，于大鼠右踝關(guān)節(jié)背側(cè)關(guān)節(jié)腔注射3%尿酸鈉（MSU）溶液100 μL制備痛風(fēng)性關(guān)節(jié)炎模型，對(duì)照組注射生理鹽水。檢測大鼠足踝關(guān)節(jié)的腫脹率，ELISA法檢測血清白細(xì)胞介素-6（IL-6）、腫瘤壞死因子-α（TNF-α）水平。結(jié)果 分析得到新加白虎湯與痛風(fēng)性關(guān)節(jié)炎的共同靶點(diǎn)基因32個(gè)，PPI分析共得到前10個(gè)靶基因?yàn)?i>IL6、TNF、INS、MAPK、IL1B、PTGS2、PPARG、MMP9、CCL2和SIRT1。GO分析與KEGG通路分析共得到新加白虎湯可能作用于痛風(fēng)性關(guān)節(jié)炎的253個(gè)生物學(xué)過程和46條相關(guān)通路，前5個(gè)生物學(xué)過程分別為凋亡信號(hào)通路的負(fù)調(diào)控、急性炎癥反應(yīng)、細(xì)胞對(duì)活性氧的反應(yīng)、炎癥反應(yīng)的正調(diào)控、與免疫反應(yīng)有關(guān)的細(xì)胞因子的產(chǎn)生；前5個(gè)通路分別為IL-17信號(hào)通路、TNF信號(hào)通路、糖尿病的AGE-RAGE信號(hào)通路、HIF-1信號(hào)通路、C型凝集素受體信號(hào)通路。與模型組比較，新加白虎湯組足踝關(guān)節(jié)腫脹率顯著降低（P<0.05），血清IL-6、TNF-α水平顯著降低（P<0.05）。結(jié)論 新加白虎湯可能通過調(diào)節(jié)炎癥反應(yīng)、氧化應(yīng)激、凋亡等對(duì)痛風(fēng)性關(guān)節(jié)炎起到治療作用，新加白虎湯能夠改善痛風(fēng)性關(guān)節(jié)炎模型大鼠足踝關(guān)節(jié)腫脹率，降低血清IL-6、TNF-α水平。

Objective To explore the mechanism of Xinjia Baihu Decoction in regulating gouty arthritis based on the network pharmacology platform, and verify the network pharmacology results by ELISA. Methods The related drug targets of Xinjia Baihu decoction were found by the systematic pharmacological analysis platform of traditional Chinese medicine (BATMAN-TCM), and the disease targets of gouty arthritis were found by human gene database GeneCards. The component-target network of Xinjia Baihu decoction was constructed by using STRING database and Cytoscape, and the action target, biological process and related pathway of Xinjia Baihu decoction in the treatment of gouty arthritis were analyzed. Male SD rats were randomly divided into control group, model group and Xinjia Baihu Decoction (20 g·kg^-1) group, ig once a day, control group and model group were given equal volume of distilled water. Except for control group, gout arthritis model was established by injecting 3% sodium urate (MSU) solution 100 μL into the dorsal joint cavity of the right ankle of rats one hour after day 5 administration, and normal saline was injected into the control group. The swelling rate of ankle joint was detected, and the levels of serum interleukin-6 (IL-6) and tumor necrosis factor -α (TNF-α) were detected by ELISA. Results Totally 32 common target genes of Xinjia Baihu decoction and gouty arthritiswere analyzed. PPI analysis showed that the top ten target proteins were IL6, TNF, INS, MAPK, IL1B, PTGS2, PPARG, MMP9, CCL2 and SIRT1, GO analysis and KEGG pathway analysis revealed that Xinjia Baihu Decoction may have 253 biological processes and 46 related pathways that may act on gouty arthritis. The first five biological processes were negative regulation of apoptotic signaling pathway, acute inflammatory response, cellular response to reactive oxygen species, positive regulation of inflammatory response, cytokine production involved in immune response. The first five pathways were IL-17 signaling pathway, TNF signaling pathway, AGE-RAGE signaling pathway in diabetic, HIF-1 signaling pathway, C-type lectin receptor signaling pathway. Compared with model group, the swelling rate of ankle joint in Xinjia Baihu Decoction group was significantly decreased (P < 0.05), and the levels of IL-6 and TNF-α in serum were significantly decreased (P < 0.05). Conclusion Xinjia Baihu decoction may have a therapeutic effect on gouty arthritis by regulating inflammation, oxidative stress, and apoptosis, and it is also confirmed that Xinjia Baihu decoction can improve the swelling rate of ankle joints in rats with gouty arthritis and reduces the levels of inflammatory factors IL-6 and TNF-α.

R285.5

海南省衛(wèi)生健康行業(yè)科研項(xiàng)目（20A200150）