利用网络药理学与分子对接方法，系统探讨济生肾气丸治疗慢性肾衰竭(chronic renal failure，CRF)的机制。

第一步，成分与靶点筛选：通过中药系统药理学(Traditional Chinese Medicine Systems Pharmacology，TCMSP)数据库、高通量实验与参考生物信息(High-throughput Experiment and Referenced Bioinformatics，HERB)数据库，筛选济生肾气丸的活性成分及其作用靶点；再利用基因卡片(GeneCards)数据库、在线人类孟德尔遗传(Online Mendelian Inheritance in Man，OMIM)数据库、疾病基因网络(Disease Gene Network，DisGeNET)数据库，获取CRF的相关疾病靶点，筛选药物与疾病的交集靶点。第二步，网络构建与富集分析：利用相互作用基因/蛋白质检索搜索工具(Search Tool for Retrieval of Interacting Genes/Proteins，STRING)数据库构建蛋白质-蛋白质相互作用网络以筛选核心靶基因，并运用Cytoscape软件构绘"中药-成分-靶点-疾病"网络；随后进行基因本体(Gene Ontology，GO)数据库功能富集分析、京都基因与基因组百科全书(Kyoto Encyclopedia of Genes and Genomes，KEGG)数据库通路富集分析。第三步，分子对接验证：采用AutoDock Vina软件对关键活性成分与核心靶点进行分子对接验证。

共筛选出济生肾气丸102个活性成分，对应232个潜在作用靶点。CRF相关靶点共2 153个，药物-疾病交集靶点138个。网络分析结果显示，槲皮素、山奈酚、汉黄芩素、黄芩素及油酸等为关键活性成分；核心靶点主要包括AKT1、TNF、IL6、MAPK1、TP53、CASP3和BCL2等。GO功能富集分析提示，相关靶点主要参与炎症反应、氧化应激、细胞凋亡及免疫调节等生物学过程。KEGG通路富集分析显示，相关通路主要涉及AGE-RAGE、TNF、IL-17、PI3K-Akt及脂质与动脉粥样硬化等。分子对接结果表明，关键活性成分与核心靶点之间具有良好的结合亲和力。

济生肾气丸可能通过槲皮素、山奈酚等黄酮类活性成分，调控AKT、MAPK、TNF等关键靶点，介导AGE-RAGE、PI3K-Akt等多条信号通路，从而在抗炎、抗氧化、抑制细胞凋亡及免疫调节等方面发挥延缓CRF进展的作用，体现了中药复方多成分、多靶点、多通路整体调控的治疗优势，为进一步研究其作用机制提供理论依据。

To systematically investigate the mechanism of Jisheng Shenqi Pills (JSP) in treating chronic renal failure (CRF) with network pharmacology and molecular docking methods.

Step 1, Component and target screening: The active ingredients and their corresponding targets of JSP were screened using the Traditional Chinese Medicine Systems Pharmacology (TCMSP) database and the High-throughput Experiment and Referenced Bioinformatics (HERB) database. Disease-related targets for CRF were retrieved from the Gene Cards (GeneCards), Online Mendelian Inheritance in Man (OMIM), and Disease Gene Network (DisGeNET) databases. And the intersecting targets between the drugs and the disease were identified. Step 2, Network construction and enrichment analysis: The protein-protein interaction (PPI) network was constructed using the Search Tool for Retrieval of Interacting Genes/Proteins (STRING) database to identify core target genes. And the "herb-component-target-disease" network was visualized using the Cytoscape software. Functional enrichment analysis was then performed with the Gene Ontology (GO) database, and pathway enrichment with the Kyoto Encyclopedia of Genes and Genomes (KEGG) database. Step 3, Validation by molecular docking: The molecular docking validation between the key active ingredients and core targets was performed using the AutoDock Vina software.

A total of 102 active ingredients of JSP were identified, corresponding to 232 potential targets. A total of 2, 153 targets were associated with CRF, resulting in 138 overlapping targets between the drug and the disease. Network analysis revealed that quercetin, kaempferol, wogonin, baicalein, and oleic acid were the key active ingredients. The core targets primarily included AKT1, TNF, IL6, MAPK1, TP53, CASP3, and BCL2. GO analysis suggested that the targets were mainly involved in inflammation, oxidative stress, apoptosis, and immune regulation. KEGG analysis showed enrichment in pathways related to AGE-RAGE, TNF, IL-17, PI3K-Akt, and lipids-atherosclerosis. Molecular docking confirmed the strong binding affinity between key components and core targets.

JSP may delay CRF progression by regulating key targets (AKT, MAPK, TNF) and signaling pathways (AGE-RAGE, PI3K-Akt) via flavonoid ingredients (quercetin, kaempferol), thereby exerting anti-inflammatory, antioxidant, inhibiting-apoptosis, and immunomodulatory effects. This illustrates the multi-component, multi-target, and multi-pathway advantages of traditional Chinese medicine (TCM) formulas, providing a theoretical basis for further mechanistic studies.