目的 基于网络药理学方法和体外实验探讨西洋参-三七药对治疗心肌梗死的作用机制。方法 （1）通过 TCMSP 数据库筛选西洋参-三七药对的活性成分，Swiss Target Prediction 数据库收集药物成分相关靶点。利用 DisGeNET、GeneCards、OMIM 数据库挖掘疾病靶点，并通过 VENNY 2.1.0 平台取药物活性成分靶点与心肌梗 死疾病相关靶点的交集靶点，筛选出西洋参-三七药对治疗心肌梗死的潜在作用靶点。借助 STRING 数据库与 Cytoscape 3.9.0 软件构建西洋参-三七药对治疗心肌梗死的蛋白互作（PPI）网络，运用 R 语言对西洋参-三七药 对治疗心肌梗死的潜在作用靶点进行 GO 功能与 KEGG 通路富集分析，并使用 AutoDockTools4 进行分子对接验 证。（2）将 20 只大鼠分为空白组及西洋参-三七药对低（1.25 g·kg-1 ）、中（2.50 g·kg-1 ）、高（5 g·kg-1 ）剂量组各 5 只，制备大鼠西洋参-三七药对低、中、高剂量含药血清及空白血清。将大鼠胚胎心肌细胞（H9c2）分为正常 组（10% 空白血清）、模型组（10% 空白血清）及中药低剂量组（10% 西洋参-三七药对低剂量含药血清）、中剂量 组（10% 西洋参-三七药对中剂量含药血清）、高剂量组（10% 西洋参-三七药对高剂量含药血清）组，进行缺氧 造模和相应含药血清干预。采用微板法检测 H9c2 细胞 LDH 含量；流式细胞术检测 H9c2 细胞凋亡及线粒体膜 电位水平；Western Blot 法检测磷酸化蛋白激酶 B （p-Akt）、蛋白激酶 B（Akt）、过氧化物酶体增殖物激活受体 γ（PPARγ）、前列腺素内过氧化物合酶 2（PTGS2）、肿瘤坏死因子 α（TNF-α）蛋白表达水平。结果 （1）共筛 选出西洋参-三七药对 19 个活性成分和 121 个治疗靶点，其中槲皮素、罂粟碱、人参皂苷 Rh2 等是其主要成 分，Akt1、PPARγ、PTGS2、TNF 是其治疗心肌梗死的关键靶点。GO 功能富集分析得到 287 条生物过程条目、 27 条细胞组分条目、53 条分子功能条目；KEGG 通路富集分析获得 122 条通路，涉及脂质和动脉粥样硬化通 路等。分子对接结果表明，槲皮素、罂粟碱、人参皂苷 Rh2 等成分与 Akt1、PPARγ、PTGS2、TNF 等靶点结 合良好。（2）与正常组比较，模型组细胞形态改变，细胞间隙变宽、排列疏松，可见大量成团的漂浮高亮死亡 细胞。与模型组比较，各中药组细胞呈梭形，细胞间隙缩小、排列较为紧密，少量漂浮高亮死亡细胞。与正常 组比较，模型组细胞 LDH 活性、细胞凋亡率及 PTGS2、TNF-α 蛋白表达显著升高（P＜0.05，P＜0.01，P＜ 0.001），线粒体膜电位及 p-Akt/Akt、PPARγ 蛋白表达显著降低（P＜0.05，P＜0.01）。与模型组比较，中药低、 中、高剂量组细胞 LDH 活性、细胞凋亡率、线粒体膜电位显著下降（P＜0.05，P＜0.01），中药中、高剂量组 PTGS2、TNF-α 蛋白表达显著降低（P＜0.05，P＜0.01）；p-Akt/Akt 和 PPARγ 蛋白表达显著升高（P＜0.05， P＜0.01）。结论 西洋参-三七药对能通过槲皮素、罂粟碱、人参皂苷 Rh2 等多种活性成分，调控脂质和动脉 粥样硬化等信号通路，减轻缺氧诱导的 H9c2 细胞损伤，发挥抗心肌梗死的作用。

Objective To explore the mechanism of Panacis Quinquefolii Radix-Notoginseng Radix et Rhizoma drug pair in the treatment of myocardial infarction based on network pharmacology and in vitro experiments. Methods （1）The TCMSP database was used to screen the active ingredients of Panacis Quinquefolii Radix-Notoginseng Radix et Rhizoma drug pair，and the Swiss Target Prediction database was used to collect drug-related targets. DisGeNET，GeneCards and OMIM databases were used to mine disease targets，and the intersection targets of drug active ingredient targets and myocardial infarction disease-related targets were taken through VENNY 2.1.0 platform to screen out the potential targets of Panacis Quinquefolii Radix-Notoginseng Radix et Rhizoma drug pair in the treatment of myocardial infarction. With the help of STRING database and Cytoscape 3.9.0 software， the protein-protein interaction （PPI） network of Panacis Quinquefolii Radix-Notoginseng Radix et Rhizoma drug pair in the treatment of myocardial infarction was constructed. R language was used to analyze the GO function and KEGG pathway enrichment of the potential targets of Panacis Quinquefolii Radix-Notoginseng Radix et Rhizoma drug pair in the treatment of myocardial infarction， and AutoDockTools4 was used for molecular docking verification.（2） Twenty rats were divided into blank group， low- （1.25 g·kg-1 ），medium-（2.50 g·kg-1 ） and high-dose （5 g·kg-1 ） groups of Panacis Quinquefolii Radix-Notoginseng Radix et Rhizoma drug pair，with 5 rats in each group. The low-，medium- and high-dose serum containing Panacis Quinquefolii Radix-Notoginseng Radix et Rhizoma drug pair and blank serum were prepared. The rat embryonic myocardial cells （H9c2） were divided into normal group （10% blank serum），model group （10% blank serum），lowdose group of Chinese medicine （10% Panacis Quinquefolii Radix-Notoginseng Radix et Rhizoma drug pair low-dose containing serum），medium-dose group of Chinese medicine （10% Panacis Quinquefolii Radix-Notoginseng Radix et Rhizoma drug pair medium-dose containing serum）， and high-dose group of Chinese medicine （10% Panacis Quinquefolii Radix-Notoginseng Radix et Rhizoma drug pair high-dose containing serum），and hypoxia modeling and corresponding drug-containing serum intervention were performed. The LDH content of H9c2 cells was detected by microplate method. The apoptosis level and mitochondrial membrane potential of H9c2 cells were detected by flow cytometry. The protein expression levels of phosphorylated protein kinase B （p-Akt）， protein kinase B （Akt）， peroxisome proliferator-activated receptor γ（PPARγ）， prostaglandin endoperoxide synthase 2（PTGS2） and tumor necrosis factor α（TNF-α） were detected by Western Blot method. Results （1） A total of 19 active components and 121 targets of Panacis Quinquefolii Radix-Notoginseng Radix et Rhizoma drug pair were screened， among which quercetin，papaverine and ginsenoside Rh2 were the main components. Akt1，PPARγ，PTGS2 and TNF are the key targets for the treatment of myocardial infarction. GO functional enrichment analysis obtained 287 biological process items，27 cellular component items，and 53 molecular function items；KEGG pathway enrichment analysis obtained 122 pathways，involving lipid and atherosclerosis pathways. The results of molecular docking showed that quercetin， papaverine and ginsenoside Rh2 had good binding with Akt1，PPARγ，PTGS2 and TNF targets.（2） Compared with the normal group，the cell morphology of the model group was changed，the cell gap was widened，the arrangement was loose，and a large number of floating and high-lighted dead cells were seen. Compared with the model group，the cells in each Chinese medicine group were spindle-shaped， the cell gap was narrowed， the arrangement was more compact，and a small amount of floating high-lighted dead cells. Compared with the normal group，the LDH activity， apoptosis rate and the protein expressions of PTGS2 and TNF-α in the model group were significantly increased （P＜ 0.05，P＜0.01，P＜0.001），and the mitochondrial membrane potential and the protein expressions of p-Akt/Akt and PPARγ were significantly decreased （P＜0.05， P＜0.01）. Compared with the model group， the LDH activity， apoptosis rate and mitochondrial membrane potential of the low-，medium- and high- dose groups of Chinese medicine significantly decreased （P＜0.05，P＜0.01），and the protein expressions of PTGS2 and TNF-α in the medium- and high- dose groups of Chinese medicine were significantly decreased （P＜0.05，P＜0.01）. The protein expressions of pAkt/Akt and PPARγ in the medium- and high- dose groups were significantly increased （P＜0.05， P＜0.01）. Conclusion Panacis Quinquefolii Radix-Notoginseng Radix et Rhizoma drug pair may regulate lipid and atherosclerosis signaling pathways through quercetin， papaverine， ginsenoside Rh2 and other active ingredients， reduce hypoxiainduced H9c2 cell injury，and play an anti-myocardial infarction role.

R542.22

中医药国际合作专项（XDZYJZC-001）；省部共建中医湿证国家重点实验室开放课题（SZ2021KF07）。