目的 基于网络药理学及分子对接探讨养血清脑颗粒（四物汤加味）治疗高血压的作用机制。方法 以课 题组前期对养血清脑颗粒的化学成分分析结果作为活性化合物筛选的基础，以口服生物利用度≥30% 及类药 性≥0.18 为筛选条件，结合文献补充入血成分。利用 TCMSP 平台、化学专业数据库和 SWISS 数据库预测养血 清脑颗粒潜在活性化合物的作用靶点。通过 GeneCards 及 DiGSeE 数据库获得高血压疾病相关靶点。将高血压 疾病相关靶点与养血清脑颗粒潜在活性化合物的作用靶点取交集（共同靶点），即为养血清脑颗粒治疗高血压的 潜在作用靶点。将潜在作用靶点与养血清脑颗粒的潜在活性化合物进行匹配，得养血清脑颗粒的降压活性化合 物。通过 STRING 数据库对养血清脑颗粒治疗高血压的潜在作用靶点进行 PPI 分析，并根据度值筛选出核心靶 点。采用 DAVID 数据库对核心靶点进行 GO 功能及 KEGG 通路富集分析。选择度值排前 6 位的核心靶点作为 对接靶蛋白，分别与降压活性化合物进行分子对接验证。结果 得到养血清脑颗粒 32 个潜在活性化合物， 161 个活性化合物作用靶点，1 539 个高血压疾病相关靶点，取交集后得到 88 个养血清脑颗粒治疗高血压的潜 在作用靶点（共有靶点），涉及 29 个降压活性化合物。PPI 分析筛选出 14 个核心靶点：PPARG、ACHE、IL4、 CCL2、JUN、NOS3、APP、IL1B、CAT、PTGS2、CASP3、TP53、TNF、IL6，涉及 158 个 GO 条目、13 条信号 通路。通过分子对接得到绿原酸、迷迭香酸、芍药苷、儿茶酸、芦荟大黄素等 5 个关键活性成分，分别与 PTGS2、CASP3、TNF、CAT、TP53、IL6 结合稳定。结论 养血清脑颗粒可能通过绿原酸、迷迭香酸等关键活 性成分，作用于 PTGS2、CASP3 等核心靶点，调控 TNF 信号通路、MAPK 信号通路、Toll 样受体信号通路等 关键通路，通过抗炎作用发挥治疗高血压的作用。

Objective To explore the mechanism of Yangxue Qingnao Granules （Siwu Decoction modified） in the treatment of hypertension based on network pharmacology and molecular docking. Methods The chemical composition analysis results of Yangxue Qingnao Granules in the early stage of the research group were used as the basis for the screening of active compounds. The oral bioavailability ≥ 30 % and drug-likeness ≥ 0.18 were used as the screening conditions， and the blood components were supplemented in combination with the literature. TCMSP， chemical professional database and SWISS database were used to predict the targets of potential active compounds of Yangxue Qingnao Granules. Hypertension-related targets were obtained through GeneCards and DiGSeE databases. The intersection of the targets related to hypertension disease and the targets of the potential active compounds of Yangxue Qingnao Granules （common targets） is the potential target of Yangxue Qingnao Granules for the treatment of hypertension. The potential targets were matched with the potential active compounds of Yangxue Qingnao Granules to obtain the antihypertensive active compounds of Yangxue Qingnao Granules. PPI analysis was performed on the potential targets of serum brain granules in the treatment of hypertension through the STRING database，and the core targets were screened according to the degree value. The David database was used to analyze the GO function and KEGG pathway enrichment of the core targets. The core targets with the top six degrees were selected as the docking target proteins， and molecular docking verification was performed with the antihypertensive active compounds. Results A total of 32 potential active compounds， 161 active compound targets and 1 539 hypertension-related targets were obtained. After intersection，88 potential targets （common targets） of Yangxue Qingnao Granules in the treatment of hypertension were obtained，involving 29 antihypertensive active compounds. PPI analysis screened 14 core targets：PPARG，ACHE，IL4，CCL2，JUN，NOS3，APP，IL1B，CAT，PTGS2，CASP3，TP53，TNF， IL6，involving 158 GO entries and 13 signaling pathways. Five key active ingredients，chlorogenic acid，rosmarinic acid， paeoniflorin catechinic acid and aloe emodin， were obtained by molecular docking， which were combined with PTGS2，CASP3，TNF，CAT，TP53 and IL6，respectively. Conclusion Yangxue Qingnao Granules may act on core targets such as PTGS2 and CASP3 through key active components such as chlorogenic acid and rosmarinic acid， regulate key pathways such as TNF signaling pathway， MAPK signaling pathway and Toll-like receptor signaling pathway，and play a role in the treatment of hypertension through anti-inflammatory effects.

R285.5；R857.3

国家科技重大专项重大新药创制——“中医药优势领域的创新中药关键技术开发研究”（2017ZX09301005）