基于网络药理学探讨补中益气汤治疗糖尿病胃轻瘫的作用机制

目的 基于网络药理学方法探讨补中益气汤治疗糖尿病胃轻瘫（Diabetic gastroparesis,DGP）的作用机制。方法 利用中药系统药理学成分分析平台（BATMAN-TCM）数据库获取补中益气汤的活性成分和作用靶点。从GEO数据库、DisGeNET数据库、GenCLiP 3数据库、GeneCards数据库以及TTD数据库收集DGP相关基因。将补中益气汤作用靶点和DGP相关基因取交集，得到补中益气汤治疗DGP的潜在靶点。利用Cytoscape3.7.1 软件构建中药活性成分-DGP靶点网络。运用STRING数据库分析交集基因所编码蛋白之间的相互作用，利用Cytoscape3.7.1 软件对结果进行可视化。利用Cytoscape软件中的ClueGO插件、CluePedia插件分别对交集靶点基因进行GO富集分析、KEGG通路富集分析及可视化。结果 筛选得到补中益气汤的185个活性成分，作用于130个DGP靶点基因，其中关键靶点10个，包括INS、AKT1、IL6、NOS3 和 AR等。GO功能和KEGG通路富集分析显示，补中益气汤可能通过抑制凋亡、自噬、氧化应激、炎症反应，调节胰岛素、血糖水平，改善胃肠道平滑肌细胞和ICC损伤，以影响DGP的发生发展。结论 本研究初步揭示了补中益气汤通过多成分-多靶点-多通路治疗DGP的作用机制，为后续更加深入研究补中益气汤的药效和作用机制提供研究方向和理论依据。

Study on the Mechanism of Buzhong Yiqi Decoction in Treating Diabetic Gastroparesis Based on Network Pharmacology

OBJECTIVE To explore the possible mechanism of Buzhong Yiqi Decoction in treating Diabetic Gastroparesis(DGP) based on network pharmacology. METHODS The active components and target genes of Buzhong Yiqi Decoction were obtained from Bioinformatics Analysis Tool for Molecular Mechanism of Traditional Chinese Medicine(BATMAN-TCM). The DGP-related genes were collected from GEO database, GenCLiP 3 database, GeneCards database and TTD database. Taking the intersection of Buzhong Yiqi decoction target genes and DGP-related genes as the potential targets of Buzhong Yiqi decoction in the treatment of DGP. Cytoscape 3.7.1 software was used to construct the network of active components of TCM and DGP-related targets. String database was used to analyze the interaction among the proteins encoded by the intersection target genes, and the results were visualized by the Cytoscape 3.7.1 software. The Cytoscape ClueGO, CluePedia plug-in were used for the Gene Ontology (GO) analysis and Kyoto Encyctopedia of Genes and Genomes (KEGG) pathway enrichment analysis of intersection target genes. RESULTS 185 active components of Buzhong Yiqi Decoction were selected, acting on 130 DGP-related target genes, 10 of which were key targets, involving INS, AKT1, IL6, NOS3, AR and so on. GO function and KEGG pathway enrichment analysis clarified that Buzhong Yiqi Decoction may affect the occurrence and development of DGP by inhibiting apoptosis, autophagy, oxidative stress and inflammation, regulating insulin and blood glucose levels, improving gastrointestinal smooth muscle cells and ICC injury. CONCLUSION This study preliminarily revealed the mechanism of Buzhong Yiqi Decoction in the treatment of DGP through multi-components, multi-targets and multi-pathways, and provided research direction and theoretical basis for further study on the efficacy and mechanism of Buzhong Yiqi Decoction.