基于网络药理学与分子对接技术分析罗氏肾病Ⅲ号方治疗非透析慢性肾病的作用机制

Analysis of the Mechanism of Action of Luoshi Shenbing No. 3 Prescription in the Treatment of Non-Dialysis Chronic Kidney Disease Based on Network Pharmacology and Molecular Docking Technology

摘要:

目的：基于网络药理学与分子对接技术分析中药复方罗氏肾病Ⅲ号方治疗非透析慢性肾病（NDCKD）的潜在机制。方法：基于中药系统药理学数据库与分析平台（TCMSP） 筛选罗氏肾病Ⅲ号方的主要活性成分及其潜在靶点；从GEO数据库（GSE93798） 提取CKD相关表达数据，筛选差异表达基因，并与药物靶点取交集。采用STRING数据库构建蛋白互作（PPI） 网络，利用Cytoscape进行网络可视化和模块分析，筛选核心靶点。使用clusterProfiler包进行基因本体（GO） 功能注释及京都基因与基因组百科全书（KEGG） 通路富集分析，揭示其生物学功能与信号通路。最终采用AutoDockTools与AutoDock Vina对主要活性成分与核心靶点进行分子对接验证。结果：共筛选出93种有效成分与209个潜在靶点，与差异基因交集后获得19个关键靶点。PPI网络分析得到表皮生长因子（EGF）、选择素E （SELE）、基质金属蛋白酶2 （MMP2）、基质金属蛋白酶1（MMP1） 和Ⅰ型胶原α1链（COL1A1） 为核心靶点。主要活性成分为槲皮素、山柰酚、木犀草素。GO分析结果显示主要富集于炎症反应、免疫调控及细胞外基质重塑相关功能，主要参与白细胞迁移、细胞外基质组织等过程。KEGG分析主要涉及糖尿病并发症中的晚期糖基化终末产物-受体（AGE-RAGE）、缺氧诱导因子-1（HIF-1）、雌激素等信号通路。分子对接结果显示，主要活性成分与核心靶点分子对接结合能均低于-5.0 kcal/mol，MMP2与山柰酚、木犀草素结合能最低为-8.82 kcal/mol。结论：罗氏肾病Ⅲ号方可能通过槲皮素、山柰酚、木犀草素等活性成分协同作用于EGF、SELE、MMP2等核心靶点，调控炎症、氧化应激与基质重塑等关键通路，发挥防治ND-CKD的作用。

Abstract:

Abstract： Objective： To analyze the potential mechanism of action of the Chinese medicine compound Luoshi Shenbing No. 3 Prescription in the treatment of non-dialysis chronic kidney disease （ND-CKD） based on network pharmacology and molecular docking technology. Methods：The primary active components and their potential targets of Luoshi Shenbing No.3 Prescription were screened using the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCMSP）. ND-CKD-related expression data were obtained from the Gene Expression Omnibus（ GEO） database（ accession number：GSE93798）. Differentially expressed genes（ DEGs） were identified and intersected with drug targets. A protein-protein interaction （PPI） network was constructed using the Search Tool for the Retrieval of Interacting Genes/Proteins （STRING） database. Network visualization and module analysis were performed using Cytoscape to identify core targets. Gene Ontology （GO） functional annotation and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment analysis were conducted using the clusterProfiler package to elucidate biological functions and signaling pathways. Finally，molecular docking validation between core components and targets was performed using AutoDockTools and AutoDock Vina. Results：A total of 93 active components and 209 potential targets were screened，and 19 key targets were obtained after intersection with DEGs. PPI network analysis identified epidermal growth factor （EGF），selectin E （SELE），matrix metalloproteinase 2 （MMP2），matrix metalloproteinase 1（ MMP1），and collagen type Ⅰ alpha 1 chain（ COL1A1） as core targets. The main active components were quercetin， kaempferol， and luteolin. GO analysis showed enrichment in functions related to inflammatory response， immune regulation， and extracellular matrix remodeling， primarily involving processes such as leukocyte migration and extracellular matrix organization. KEGG analysis primarily involved the advanced glycation end product-receptor for advanced glycation end product （AGE-RAGE） signaling pathway in diabetic complications， the hypoxia-inducible factor-1 （HIF-1） signaling pathway， and the estrogen signaling pathway. Molecular docking results showed that the binding energies of the main active components with core targets were all less than -5.0 kcal/mol， with the lowest binding energy of -8.82 kcal/mol observed between MMP2 and kaempferol and luteolin. Conclusion：Luoshi Shenbing No.3 Prescription may act synergistically through active components such as quercetin， kaempferol， and luteolin on core targets including EGF， SELE， and MMP2， thereby regulating key pathways such as inflammation， oxidative stress，and matrix remodeling，thus exerting preventive and therapeutic effects against ND-CKD.