网络药理学结合转录组学方法探究加味祛瘀护膜剂治疗反流性食管炎作用靶点

Exploration of Therapeutic Targets of Modified Quyu Humo Mixture for Reflux Esophagitis via Network Pharmacology Combined with Transcriptomics

摘要: 目的：基于网络药理学及转录组学方法探讨加味祛瘀护膜剂治疗反流性食管炎的作用靶点。方法：收集网络药理学和转录组学的共同靶点，进行KEGG功能富集分析。构建PPI网络图并进行网络拓扑分析，确定潜在核心靶点。构建通路–靶点网络图，确定发挥关键作用的信号通路。结果：通过KEGG富集分析、PPI分析、拓扑分析等得到6个潜在核心靶点(SRC、GSK3B、RXRA、RAF1、RPS6KB、PPARA)，以及9个主要信号通路(FAK信号通路、ErbB信号通路、Rap1信号通路、mTOR信号通路、PI3K-Akt信号通路、cAMP信号通路、VEGF信号通路、MAPK信号通路、FoXO信号通路)。结论：通过网络药理学与转录组学研究发现加味祛瘀护膜剂中的活性成分起到治疗反流性食管炎的作用机制可能为：通过SRC、GSK3B、RXRA、RAF1、RPS6KB、PPARA这6个核心靶点介导多个通路抑制炎症、细胞增殖，进而改善炎症反应、阻止RE的进一步进展。以期为后续加味祛瘀护膜剂抗反流性食管炎的药理学研究和临床应用提供理论依据与参考线索。

Abstract: Objective: To explore the therapeutic targets of Modified Quyu Humo Decoction in the treatment of reflux esophagitis based on network pharmacology and transcriptomics. Methods: Common targets shared by network pharmacology prediction and transcriptomic data were collected for KEGG functional enrichment analysis. A protein-protein interaction (PPI) network was constructed and subjected to network topological analysis to screen potential core targets. A pathway-target network was established to identify the pivotal signaling pathways involved. Results: Six potential core targets (SRC, GSK3B, RXRA, RAF1, RPS6KB, PPARA) and nine major signaling pathways (FAK signaling pathway, ErbB signaling pathway, Rap1 signaling pathway, mTOR signaling pathway, PI3K-Akt signaling pathway, cAMP signaling pathway, VEGF signaling pathway, MAPK signaling pathway, FoxO signaling pathway) were identified via KEGG enrichment analysis, PPI network analysis and topological analysis. Conclusion: Combined network pharmacology and transcriptomic analyses revealed that the active ingredients in Modified Quyu Humo Decoction exert therapeutic effects against reflux esophagitis through a potential mechanism: regulating the six core targets (SRC, GSK3B, RXRA, RAF1, RPS6KB, PPARA) to mediate multiple signaling pathways, inhibit inflammation and abnormal cell proliferation, alleviate inflammatory responses, and hinder the progression of reflux esophagitis (RE). This study provides theoretical basis and research clues for subsequent pharmacological research and clinical application of Modified Quyu Humo Decoction against reflux esophagitis.