目的采用网络药理学结合动物实验探究补阳还五汤治疗冠状动脉微血管疾病（CMD）的潜在机制。方法利用中药系统药理学数据库与分析平台（TCMSP）、SymMap筛选补阳还五汤活性成分，GeneCards、OMIM、TTD获取CMD靶点，构建“药物-成分-靶点”网络，进行基因本体（GO）注释及京都基因与基因组百科全书（KEGG）通路富集分析及分子对接验证。建立CMD大鼠模型，用补阳还五汤与尼可地尔干预4周，通过超声心动图评估心功能，苏木精-伊红（HE）及Masson染色观察心肌病理变化，透射电镜观察微血管内皮超微结构，免疫组化观察心脏微血管密度，免疫荧光验证缺氧诱导因子-1α（HIF-1α）通路蛋白表达情况。结果筛选出补阳还五汤活性成分62个、交集靶点148个，核心成分为槲皮素、木犀草素等，核心靶点包括白细胞介素6（IL6）、蛋白激酶B（AKT1）等，靶点富集于炎症反应、细胞凋亡相关过程及磷脂酰肌醇3-激酶（PI3K）-Akt、HIF-1等通路，分子对接显示关键成分和核心靶点结合活性良好。动物实验证实，补阳还五汤可显著提高CMD大鼠左室射血分数（LVEF）及左室短轴缩短率（FS）（P＜ 0.001），减轻心肌纤维化，修复内皮超微结构损伤，可能和增强HIF-1α/血红素氧合酶1（HO-1）通路活性有关。结论补阳还五汤通过多成分协同作用于多靶点，调控相关信号通路，保护血管内皮、减轻心肌损伤，从而治疗CMD，为临床应用提供理论支撑。

Objective To investigate the potential mechanism of Buyang Huanwu Decoction in treating coronary microvascular disease (CMD) by integrating network pharmacology with animal experiments. Methods Active components of Buyang Huanwu Decoction were screened from the TCMSP and SymMap databases. CMD-related targets were collected from GeneCards, OMIM, and TTD. A “drug-component-target” network was constructed, followed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses, and molecular docking validation. A rat CMD model was established. The model rats were treated with Buyang Huanwu Decoction or nicorandil for four weeks. Cardiac function was assessed via echocardiography, myocardial histopathology was observed using HE and Masson staining, microvascular endothelial ultrastructure was examined with transmission electron microscopy, immunohistochemistry was performed to evaluate cardiac microvascular density. Cytokine expression, and immunofluorescence verification of HIF1α pathway protein expression. Results Network pharmacology identified 62 active components and 148 intersection targets for Buyang Huanwu Decoction. Core active components included quercetin and luteolin, and core targets comprised IL6 and AKT1. The targets were significantly enriched in biological processes related to inflammation, apoptosis, and signaling pathways such as PI3K-Akt and HIF-1. Molecular docking confirmed favorable binding activity between key components and core targets. Animal experiments demonstrated that Buyang Huanwu Decoction significantly improved left ventricular ejection fraction (LVEF) and fractional shortening (FS) in CMD rats (P < 0.001), alleviated myocardial fibrosis, and repaired ultrastructural damage, which may be associated with enhanced HIF-1α/HO-1 pathway activity. Conclusion Buyang Huanwu Decoction exerts therapeutic effects on CMD through a multi-component, multi-target, and multi-pathway mechanism, involving endothelial protective and anti-myocardial injury actions. This study provides a theoretical basis for the clinical application of Buyang Huanwu Decoction.

R285.5

国家自然科学基金资助项目（8240153568）