目的 基于网络药理学探讨新加白虎汤调控痛风性关节炎的作用机制，并利用ELISA法初步验证其抗炎作用。方法 通过中药系统药理学分析平台BATMAN-TCM查找新加白虎汤的化学成分及靶点，人类基因数据库GeneCards查找痛风性关节炎的相关疾病靶点。将新加白虎汤与痛风性关节炎的交集靶点输入STRING数据库构建蛋白相互作用（PPI）网络，将得到的交集蛋白靶标基因输入Cytoscape中的ClueGo插件进行基因本体论（GO）分析和京都基因与基因组百科全书（KEGG）通路分析。SD雄性大鼠随机分为对照组、模型组和新加白虎汤（20 g·kg^-1）组，每天ig给药1次，对照组和模型组ig等体积蒸馏水。除对照组外，第5天给药后1 h，于大鼠右踝关节背侧关节腔注射3%尿酸钠（MSU）溶液100 μL制备痛风性关节炎模型，对照组注射生理盐水。检测大鼠足踝关节的肿胀率，ELISA法检测血清白细胞介素-6（IL-6）、肿瘤坏死因子-α（TNF-α）水平。结果 分析得到新加白虎汤与痛风性关节炎的共同靶点基因32个，PPI分析共得到前10个靶基因为IL6、TNF、INS、MAPK、IL1B、PTGS2、PPARG、MMP9、CCL2和SIRT1。GO分析与KEGG通路分析共得到新加白虎汤可能作用于痛风性关节炎的253个生物学过程和46条相关通路，前5个生物学过程分别为凋亡信号通路的负调控、急性炎症反应、细胞对活性氧的反应、炎症反应的正调控、与免疫反应有关的细胞因子的产生；前5个通路分别为IL-17信号通路、TNF信号通路、糖尿病的AGE-RAGE信号通路、HIF-1信号通路、C型凝集素受体信号通路。与模型组比较，新加白虎汤组足踝关节肿胀率显著降低（P<0.05），血清IL-6、TNF-α水平显著降低（P<0.05）。结论 新加白虎汤可能通过调节炎症反应、氧化应激、凋亡等对痛风性关节炎起到治疗作用，新加白虎汤能够改善痛风性关节炎模型大鼠足踝关节肿胀率，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

海南省卫生健康行业科研项目（20A200150）