【目的】 采用网络药理学技术结合体内实验验证探讨暖心胶囊治疗缺血性心力衰竭（IHF）的作用机制。【方法】 使用中 药系统药理学数据库与分析平台（TCMSP）、SwissTarget Predition数据库检索暖心胶囊的成分并预测其潜在靶点，再通过在线 人类孟德尔遗传（OMIM）和 GeneCards 数据库预测 IHF 的靶点，得到暖心胶囊和 IHF 的交集靶点，构建暖心胶囊-交集靶 点-IHF网络，筛选暖心胶囊治疗IHF的关键活性成分，通过基因/蛋白相互作用检索工具（STRING）数据库构建交集靶点的蛋 白质相互作用（PPI）网络，使用Cytoscape 3.7.2的cytoHubba插件对PPI网络进行分析得到主要靶点基团，最后通过Metascape 数据库对交集靶点进行基因本体论（GO）和京都基因与基因组百科全书（KEGG）分析。采用永久结扎冠状动脉左前降支法建立 小鼠IHF模型，干预4周后通过超声心动图评价心脏功能和结构情况，苏木精-伊红（HE）染色评价心脏组织病理情况，免疫 荧光法检测心脏淋巴管密度，蛋白质免疫印迹（Western Blot）法检测心脏组织血管内皮生长因子 C（VEGFC）、血管内皮生长 因子受体 3（VEGFR3）蛋白表达水平。【结果】 共获得暖心胶囊-IHF的交集靶点 242个，筛选出芹菜素、水黄皮素、柚皮素、 4’，5，7，8-四甲氧基黄酮、橘皮素等核心成分，筛选出4个核心分子基团，包含VEGFC、FLT4（VEGFR3）等靶点，GO分析主 要涉及细胞对氮化合物的反应、正调节细胞迁移、正调控磷代谢过程和调节炎症反应等，KEGG 通路分析主要包括癌症通 路、脂质和动脉粥样硬化和内分泌抵抗通路等。体内实验验证结果显示，暖心胶囊能有效改善IHF模型小鼠的心功能，改善 心脏组织的病理变化和炎症细胞浸润，促进淋巴管新生，提高 VEGFC、VEGFR3蛋白表达水平。【结论】 暖心胶囊可能通过 调控VEGFC/VEGFR3促进心脏淋巴管生成发挥改善IHF的作用。

Objective To investigate the therapeutic mechanism of Nuanxin Capsules （NXC） in ischemic heart failure （IHF） using network pharmacology and in vivo experimental validation. Methods Active components of NXC were retrieved from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCMSP） and SwissTargetPrediction database. Potential IHF-related targets were predicted via OMIM and GeneCards databases. Shared targets between NXC and IHF were identified to construct a “NXC-shared targetsIHF” network. Key bioactive components were screened， and protein-protein interaction （PPI） networks were built using STRING database. Core target modules were analyzed via CytoHubba plugin in Cytoscape 3.7.2. Gene Ontology （GO） and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway analyses were performed using Metascape. For in vivo validation，an IHF mouse model was established by permanent ligation of the left anterior descending coronary artery. After 4-week intervention，cardiac function/structure was assessed by echocardiography， histopathology by hematoxylin-eosin （HE） staining， lymphatic vessel density by immunofluorescence， and protein expression of vascular endothelial growth factor C （VEGFC） and vascular endothelial growth factor receptor 3（VEGFR3） by Western Blot. Results Network pharmacology identified 242 shared targets between NXC and IHF，with core components including apigenin，pongapin，naringenin，4’，5，7，8-tetramethoxyflavone，and tangeretin. Four core molecular clusters were identified （e. g.，VEGFC，FLT4/VEGFR3）. GO analysis revealed enrichment in cellular response to nitrogen compounds， positive regulation of cell migration/phosphorus metabolism，and inflammatory response modulation. KEGG pathways included cancer，lipid/atherosclerosis，and endocrine resistance pathways. In vivo experiments demonstrated that NXC significantly improved cardiac function， attenuated pathological changes and inflammatory infiltration， promoted lymphangiogenesis， and upregulated VEGFC/VEGFR3 protein expression in IHF mice. Conclusion NXC may ameliorate IHF by promoting cardiac lymphangiogenesis via VEGFC/VEGFR3 signaling.

R285.5

国家自然科学基金资助项目（编号：82305170）；广州市科技计划项目（编号：202201020318）