基于网络药理学与分子对接技术的大黄治疗糖尿病肾病多靶点作用机制研究

Study on the Multi-Target Mechanism of Rheum palmatum in Treating Diabetic Nephropathy Based on Network Pharmacology and Molecular Docking Technology

摘要: 本研究通过网络药理学与分子对接技术系统研究了大黄治疗糖尿病肾病(DKD)的多靶点作用机制。采用TCMSP数据库筛选大黄16种活性成分及56个药物靶点，整合GeneCards、OMIM和Disgenet数据库获得4301个DKD相关靶基因，通过Venny分析和R语言处理确定41个大黄治疗DKD的潜在基因靶点。利用Cytoscape 3.10.3构建“药物–成分–靶点–疾病”网络，STRING数据库建立蛋白互作网络，经CytoNCA插件分析筛选出包括TNF、TP53、HSP90AA1、CASP3、BCL2、PTGS2、ESR1和MYC在内的核心靶点。分子对接验证显示大黄活性成分与HSP90AA1、BCL2、TNF等靶点具有显著结合亲和力，GO与KEGG富集分析表明其治疗机制涉及炎症反应、细胞凋亡、氧化应激和组织纤维化等多条信号通路的调控，证实了大黄通过“多成分–多靶点–多通路”协同作用治疗DKD的科学机制。这项研究为深入理解中药治疗复杂疾病的网络调控机制提供了重要的理论依据。

Abstract: This study systematically investigated the multi-target mechanism of Rheum palmatum (rhubarb) in treating diabetic kidney disease (DKD) using network pharmacology and molecular docking techniques. Sixteen active components and 56 potential drug targets of rhubarb were identified through the TCMSP database. By integrating data from GeneCards, OMIM, and DisGeNET, 4301 DKD-related target genes were collected. Venny analysis and R software processing revealed 41 key therapeutic targets. Cytoscape 3.10.3 was employed to construct a “drug-component-target-disease” interaction network, while the STRING database was used to establish a protein-protein interaction (PPI) network. Using the CytoNCA plugin, core targets, including TNF, TP53, HSP90AA1, CASP3, BCL2, PTGS2, ESR1, and MYC, were identified. Molecular docking demonstrated strong binding affinity between rhubarb’s active components and key targets (HSP90AA1, BCL2, TNF, etc.). GO and KEGG enrichment analyses indicated that the therapeutic mechanism involves the regulation of multiple pathways, such as inflammatory response, apoptosis, oxidative stress, and tissue fibrosis, confirming rhubarb’s “multi-component, multi-target, multi-pathway” synergistic effect on DKD. This research provides critical theoretical insights into the network regulation mechanisms of traditional Chinese medicine (TCM) in treating complex diseases, supporting the scientific rationale for using rhubarb in DKD therapy.