基于网络药理学和分子对接探讨金匮肾气丸治疗膀胱过度活动症的作用机制

Exploring the Mechanism of Jingui Shenqi Pill in the Treatment of Overactive Bladder Based on Network Pharmacology and Molecular Docking

摘要: 目的：针对膀胱过度活动症，从中药方剂金匮肾气丸出发，借助网络药理学与分子对接，解析其候选成分、枢纽靶点及可能路径。方法：按OB ≥ 30%、DL ≥ 0.18自TCMSP筛选方中八味药的活性成分，SMILES取自PubChem，以SwissTargetPrediction预测靶点；从OMIM、GeneCards获取疾病靶点并作映射。Cytoscape构建“药物–活性成分–靶点”网络并提取关键活性成分；STRING构建蛋白质相互作用(PPI)网络，CytoHubba筛出前10个核心靶点；Metascape行GO、KEGG富集；PyMOL清理受体后，以AutoDock Vina将前5个成分与核心靶点对接。结果：得到125个成分、1040个预测靶点，疾病靶点4540个，交集714个。药物–成分–靶点网络含848个节点、9552条边，PPI含713个节点、19,016条边。获取包含Ethyl Linolenate、Peroxyergosterol和Campesterol等5个关键成分以及包含AKT1、TP53、IL6、MTOR与TRPV1等10个核心靶点。生物过程3228条、细胞组分269条、分子功能604条；KEGG 263条，靠前为钙信号、神经递质受体耦联、MAPK、PI3K-Akt及肌动蛋白丝重排。关键成分与核心靶点对接良好，亲和性高。结论：金匮肾气丸可能通过调控钙离子信号通路和丝裂原活化蛋白激酶等信号通路，作用于TRPV1、TRPM8、AKT1等核心靶点，治疗膀胱过度活动症。

Abstract: Objective: To analyze, for overactive bladder, the candidate ingredients, hub targets, and potential pathways of the Chinese herbal formula Jingui Shenqi Pill by network pharmacology and molecular docking. Methods: Active ingredients of the eight herbs in the formula were screened from TCMSP with oral bioavailability (OB) ≥ 30% and drug-likeness (DL) ≥ 0.18. SMILES were retrieved from PubChem, and targets were predicted using SwissTargetPrediction. Disease-related targets were collected from OMIM and GeneCards and then mapped. A drug-active ingredient-target network was constructed in Cytoscape, and key active ingredients were extracted. A protein-protein interaction (PPI) network was built with STRING, and the top 10 core targets were screened using CytoHubba. GO and KEGG enrichment analyses were performed with Metascape. After receptor preparation in PyMOL, the top five ingredients were docked to the core targets using AutoDock Vina. Results: A total of 125 ingredients and 1040 predicted targets were obtained; 4540 disease-related targets were collected, with 714 overlapping targets. The drug-ingredient-target network contained 848 nodes and 9552 edges, and the PPI network contained 713 nodes and 19,016 edges. Five key ingredients, including ethyl linolenate, peroxyergosterol, and campesterol, and 10 core targets, including AKT1, TP53, IL6, MTOR, and TRPV1, were identified. GO analysis yielded 3228 biological processes, 269 cellular components, and 604 molecular functions. KEGG analysis identified 263 pathways, among which calcium signaling, neurotransmitter-receptor coupling, MAPK, PI3K-Akt, and actin filament rearrangement ranked high. The key ingredients docked well with the core targets and showed high binding affinity. Conclusion: Jingui Shenqi Pill may treat overactive bladder by regulating signaling pathways such as the calcium signaling pathway and mitogen-activated protein kinase, and by acting on core targets including TRPV1, TRPM8, and AKT1.