基于网络药理与分子对接的芪苈山萸心衰方减轻心肌梗死后心力衰竭大鼠心肌细胞损伤的潜在药效物质研究

Exploring Active Compounds of Qilishanyu Heart Failure Prescription Alleviates Myocardial Cell Injury of Heart Failure after Myocardial Infarction Based on Network Pharmacology and Molecular Docking

摘要: 目的：探讨芪苈山萸心衰方治疗心梗后心衰的潜在物质基础。方法：选取SD大鼠，随机分为五组。造模并连续灌胃4周后取心脏组织进行TTC染色和透射电镜观察心脏梗死体积和心肌细胞损伤程度。依据各类数据库查找药物活性成分及靶标，并预测疾病靶点。构建药物–成分–靶点–疾病关系网络、GO和KEGG富集分析，并进行分子对接。结果：模型组梗死体积较假手术组显著增加(P < 0.01)，线粒体数量减少，线粒体嵴断裂，肌原纤维结构模糊不清；低、高剂量组较模型组心肌梗死体积均显著减少(P < 0.01)，线粒体和肌原纤维结构基本正常。筛选活性成分159个，核心靶点82个；GO富集分析条目588个，KEGG富集分析得信号通路37条；分子对接提示豆甾醇与靶蛋白结合较好。结论：芪苈山萸心衰方中化合物可能通过与关键靶蛋白结合，调节相关信号通路，减轻心肌细胞损伤，发挥治疗作用。

Abstract: Objective: To explore the effective chemical constituents of Qilishanyu Heart Failure Prescription for treatment of Heart Failure. Methods: SD rats were randomly divided into 5 groups, with 12 rats in each group. After modeling and continuous intragastric administration for 4 weeks, the heart tissues were taken for TTC staining and transmission electron microscopy to observe the volume of cardiac infarction and the extent of myocardial cell damage and the degree of myocardial cell damage was observed by transmission electron microscopy. Active ingredients of drug and the corresponding targets were screened, while the targets of disease n were predicted according to a variety of databases. A network of drug-component-target-disease, GO and KEGG pathway enrichment analysis as well as molecular docking was conducted. Results: Compared with the sham group, the model group was observed with significantly increased myocardial infarction volume (P < 0.01), decreased of heart mitochondria, fractured of the mitochondrial cristae, and the blurred of cardiac myofibrils structure. Compared with model group, myocardial infarction volume of Qilishanyu Heart Failure Prescription formula was significantly reduced in both low and high dose groups (P < 0.01), and the mitochondrial and cardiac myofibrils structures were basically normal. A total of 159 components were screened, with 82 core targets. GO function enrichment analysis revealed 488 items. KEGG pathway enrichment screened 37 signaling pathways. The results of molecular docking showed that stigmasterol had a certain degree of affinity with proteins. Conclusion: The active ingredients in Qilishanyu Heart Failure Prescription may combine with core targets to regulate signaling pathways and reduce myocardial cell damage, which played a significant role in the treatment of Heart Failure.