目的 利用网络药理学和分子对接技术，研究芍药汤治疗溃疡性结肠炎（UC）的物质基础及其可能的作用机制。方法 利用TCMIP和TCMSP数据库挖掘芍药汤潜在活性成分及其药物靶点，通过GeneCard和OMIM数据库筛选疾病靶点。将药物靶点与疾病靶点匹配所得交集靶点导入String构建PPI网络，借助Cyto NCA插件筛选关键靶点，将关键靶点与对应成分联系起来绘制网络图，筛选关键成分；对关键靶点进行GO和KEGG富集分析。利用SYBYL-X 2.0软件对关键成分和关键靶点进行分子对接。体内复制大鼠UC模型，芍药汤干预后，观察疾病活动指数，评估结肠病理损伤，ELISA检测肿瘤坏死因子α（TNF-α）、白细胞介素4（IL-4）、趋化因子受体4（CXCR4）的水平。结果 芍药汤的潜在活性成分共有424个，关键成分包括槲皮素、棕榈酸、儿茶素、原花青素等；其治疗UC的关键靶点41个，靶点主要涉及转录的正调控、凋亡过程的负调控、信号转导等生物学过程，通过TNF、缺氧诱导因子1（HIF-1）、癌症途径、Toll样受体（TLR）、PI3K-Akt等信号通路发挥治疗UC的作用。分子对接结果显示关键成分与对应靶点具有较好的结合活性。体内实验验证，芍药汤可改善结肠病理损伤，下调TNF-α和CXCR4，上调IL-4表达。结论 芍药汤治疗UC具有“多组分-多靶点-多通路”的作用特点，该研究为进一步深入研究其作用机制奠定了基础。

Objective Network pharmacology and molecular docking technology were used to study the material basis and possible mechanism of Shaoyao Decoction in treatment of ulcerative colitis (UC). Methods TCMSP and TCMID were used to obtain the potential active components and drug targets of Shaoyao Decoction. GeneCard and OMIM were used to search disease targets. The common targets obtained by matching drug targets and disease targets were imported into String to construct a PPI network, and Cyto NCA plug-in was used to screen key targets. The network diagram was drawn by connecting the key targets with the corresponding components, so as to screen the key components. GO and KEGG enrichment analyses were performed on key targets. SYBYL-X2.0 software was used to dock the molecules of the key components with the key targets. The rat UC model was replicated in vivo. After the intervention of Shaoyao Decoction, the disease activity index was observed, the colonic pathological damage was evaluated, and the levels of TNF-α, IL-4 and CXCR4 were detected by ELISA. Results A total of 424 potential active components were found in Shaoyao Decoction. The key components included quercetin, palmitic acid, catechin, and procyanidins, etc. Its 41 key targets for UC were mainly related to the positive regulation of transcription, the negative regulation of apoptosis process, the signal transduction, and other biological processes. The key targets played a role in treating UC through signaling pathways such as TNF, HIF-1, cancer pathway, TLR, PI3K-Akt, et al. Molecular docking results showed that key components had good binding activity with corresponding targets. Shaoyao Decoction improved colon pathological damage, down-regulated the level of TNF-α and CXCR4, and up-regulated the level of IL-4 in vivo. Conclusion Shaoyao Decoction has the characteristics of "multi-components, multi-targets, multi-pathways" in treatment of UC, which lays a foundation for further study of its mechanism.

R285.5

国家自然科学基金资助项目（81573871）；浙江省中医药科技计划项目（2020ZB061）