目的 基于网络药理学和实验验证探讨瓜蒌皮注射液治疗动脉粥样硬化的作用机制。方法 检索瓜蒌皮注射液的化学成分报道，通过Swiss ADME和Swiss Target Prediction预测活性成分和靶点。通过OMIM、TTD、GeneCards数据库获得动脉粥样硬化的靶点，使用Venny 2.1软件获得瓜蒌皮注射液治疗动脉粥样硬化的共有靶点。采用Cytoscape 3.6.1软件构建“药物–成分–靶点”网络，String、DAVID数据库进行蛋白质相互作用（PPI）网络构建，基因本体（GO）、京都基因和基因组百科全书（KEGG）富集分析。通过高脂饮食建立动脉粥样硬化小鼠模型，将小鼠随机分为对照组、模型组、瓜蒌皮注射液（0.6、1.2 mL/kg）组，每组6只。瓜蒌皮注射液组分别im 0.6、1.2 mL/kg瓜蒌皮注射液，连续给药3周。全自动生化分析仪检测小鼠血脂相关指标，苏木素–伊红（HE）染色观察主动脉病理变化，蛋白质免疫印迹（Western blotting）法检测核心蛋白的表达。结果 筛选出芹菜素-7-O-β-D-葡萄糖苷、木犀草素、香草酸等21个瓜蒌皮注射液活性成分，共有靶点89个，核心靶点包括蛋白激酶B1（Akt1）、半胱氨酸天冬氨酸蛋白酶-3（Caspase-3）、非受体酪氨酸激酶（SRC）等。GO功能分析获得702个条目，KEGG富集获得42条信号通路。动物实验显示，瓜蒌皮注射液可显著降低血清总胆固醇（TC）、三酰甘油（TG）、低密度脂蛋白胆固醇（LDL-C）水平（P＜0.05、0.01）；HE染色显示，瓜蒌皮注射液可减少斑块在主动脉管壁上附着；Western blotting显示，瓜蒌皮注射液可显著升高Caspase-3蛋白表达，降低p-SRC、p-Akt1蛋白表达（P＜0.05、0.01）。结论 瓜蒌皮注射液通过多个成分调控Caspase-3、p-SRC、p-Akt1等核心靶点，降低斑块在主动脉附着，进而发挥治疗动脉粥样硬化。

Objective To investigate the mechanism of action of Gualoupi Injection in treatment of atherosclerosis based on network pharmacology and animal experiments. Methods To search the chemical composition reports of Gualoupi Injection, and predict the active constituents and targets by Swiss ADME and Swiss Target Prediction. The targets of atherosclerosis were obtained by OMIM, TTD, and GeneCards databases, and the common targets of Gualoupi Injection for the treatment of atherosclerosis were obtained by Venny 2.1 software. Cytoscape 3.6.1 software was used to construct the “drug - component - target” network, String and DAVID databases were used to construct the PPI network, GO and KEGG enrichment analysis. The atherosclerosis mouse model was established by high-fat diet, and the mice were randomly divided into control group, model group, Gualoupi Injection (0.6, 1.2 mL/kg) group, with 6 mice in each group. Gualoupi Injection group was given 0.6 and 1.2 mL/kg of Gualoupi Injection, respectively, for 3 weeks. The relevant indexes of blood lipids were detected by automatic biochemical analyzer, the pathological changes of aorta were observed by HE staining, and the expression of core proteins was detected by Western blotting. Results 21 Active components of Gualoupi Injection, including apigenin-7-O-β-D-glucoside, luteolin, and vanillic acid were selected, with 89 targets. The core targets included Akt1, Caspase 3, and SRC. GO functional analysis obtained 702 items, KEGG enrichment obtained 42 signaling pathways. Animal experiments showed that the levels of TC, TG, and LDL-C in serum could be significantly reduced by Gualoupi Injection (P＜0.05, 0.01). HE staining showed that Gualoupi Injection could reduce plaque adhesion on the active vascular wall. Western blotting showed that Gualoupi Injection significantly increased the protein expression of Caspase 3, and decreased the protein expressions of p-SRC and p-Akt1 (P＜0.05, 0.01). Conclusion Gualoupi Injection regulates Caspase 3, p-SRC, p-Akt1 and other targets through multiple components, thereby reducing blood lipids and plaque attachment, and thus treating atherosclerosis.

R285.5；R972

郑州大学第一附属医院横向课题（K2020-0233）