目的 研究瑶药四方藤小复方对类风湿性关节炎（RA）大鼠的抗炎作用，并分析四方藤小复方的作用机制，预测其质量标志物（Q-marker）。方法 SD大鼠随机分为对照组、模型组、雷公藤多苷片阳性对照组以及四方藤小复方提取物高、低剂量（28.7、7.2 g/kg）组，每组8只。除对照组外，其余各组均采用Ⅱ型胶原蛋白-完全弗氏佐剂法诱导RA大鼠模型，各给药组在造模期间ig给予相应药物，连续28 d。实验期间观察大鼠足趾红肿程度并评分，实验末采用ELISA法测定血清白细胞介素-1β（IL-1β）、肿瘤坏死因子-α（TNF-α）水平。通过TCMSP和Drugbank数据库搜索并筛选四方藤小复方的化学成分以及预测作用靶点，采用TTD数据库搜索RA疾病靶点。通过String数据库和Cytoscape软件构建和可视化靶点互作网络，通过MCODE插件聚类分析。利用String数据库进行GO和KEGG富集分析。最后结合化学成分的有效性、可测性，预测四方藤小复方的Q-marker。结果 与模型组比较，四方藤小复方提取物高、低剂量组及雷公藤多苷片组大鼠足肿胀程度明显减轻（P<0.01），血清IL-1β和TNF-α水平均显著降低（P<0.01）。RA的疾病靶点有89个，发病机制与细胞因子-受体作用通路、RA通路异常有关。四方藤小复方中筛选得到31个化学成分、化学成分的作用靶点119个，其中12个属于疾病靶点，参与刺激反应调节、细胞增殖调节、细胞代谢过程调节、细胞内信号转导的调控等1 112个生物学过程，以及调控RA通路、TNF通路等113条信号通路，最终发挥治疗RA的作用。同时预测得到岩白菜素、白藜芦醇、氯化两面针碱、蛇床子素、芳樟醇、欧前胡素、乙氧基白屈菜红碱、芹菜素、黄连碱、橙皮苷、芝麻素11个成分可作为四方藤小复方的Q-marker。结论 四方藤小复方可显著减轻RA大鼠的急性炎症，其可能通过白藜芦醇等多种成分作用于以PTGS2为主的多个靶点，参与调控RA通路、TNF通路等多条炎症免疫通路。岩白菜素、白藜芦醇、氯化两面针碱、蛇床子素、芳樟醇、欧前胡素、乙氧基白屈菜红碱、芹菜素、黄连碱、橙皮苷、芝麻素可作为用于四方藤小复方质量控制的Q-marker。

Objective To evaluate the anti-rheumatism effect, and predict the mechanism and Q-marker of YAO medicine compound containing Cissus pteroclada (Sifangteng in Chinese, SFT) in the treatment of rheumatoid arthritis (RA) in rats. Methods SD rats were randomly divided into control group, model group, tripterygium glycosides group and SFT high/low dose (28.7, 7.2 g/kg) groups with eight rats in each group. Except the control group, the RA models in rats induced by Collange Ⅱ collagen were established. The SFT group and the tripterygium glycosides group were given corresponding drugs by intragastric administration during the modeling period, while the other two groups were given the same volume of saline once daily for 28 d. The degree of foot swelling was measured and scored during the experiment. The levels of TNF-α and IL-1β in serum were measured by ELISA at the end of the experiment. SFT chemical components and predicting targets were searched and screened through TCMSP and Drugbank databases. The target of RA disease was searched by TTD database. The protein interaction network was constructed and visualized by String database and Cytoscape software, cluster analysis was analyzed by MCODE. GO and KEGG enrichment analysis was carried out using String database. Finally, combined with the validity and measurability of chemical components, the Q-marker of SFT was predicted. Results Compared with the model group, the foot swelling of rats in SFT high and low dose groups and positive group was significantly reduced (P<0.01), and the serum levels of IL-1β and TNF-α were significantly decreased (P<0.01). There were 89 disease targets of RA. The pathogenesis of RA was related to abnormal cytokine-receptor pathway and RA pathway. A total of 31 components in SFT were screened and its 119 target proteins were predicted, 12 of them belong to disease targets were involved in 1 112 biological processes, such as regulation of stimulation response, regulation of cell proliferation, regulation of cell metabolism, regulation of intracellular signal transduction, and regulation of 113 signaling pathways, such as RA pathway and TNF pathway, which ultimately play a role in the treatment of RA. At the same time, 11 components were predicted to be Q-markers of SFT, including apigenin, resveratrol, bergenin, nitidine, osthol, linalool, ammidin, ethoxychelerythrine, coptisine, hesperidin, and sesamin. Conclusion SFT can significantly reduce acute inflammation in RA rats. SFT may act on PTGS2-based targets through resveratrol and other components, and participate in regulation of RA pathway, TNF pathway and other inflammatory and immune pathways. Apigenin, resveratrol and bergenin, nitidine, osthol, linalool, ammidin, ethoxychelerythrine, coptisine, hesperidin, sesamin can be used as Q-markers for SFT quality control.

广西中医药大学2018年广西一流学科建设项目（2018XK029）；广西中医药大学2018年广西一流学科建设项目（05019042）；国家自然科学基金资助项目（81560674）；广西自然科学基金项目（2017GXNSFAA198078）；2019年广西高校中青年教师科研基础能力提升项目（2019KY0319）