加味桃核承气汤防治糖尿病胃轻瘫作用机制及网络药理学分析

目的:运用网络药理学技术分析加味桃核承气汤治疗糖尿病胃轻瘫的作用靶点和相关信号通路,进一步分析其防治糖尿病胃轻瘫的理论基础和作用机制。方法:运用中药系统药理学成分分析平台(bioinformatics analysis tool for molecular mechanism of TCM,BATMAN-TCM)数据库获取加味桃核承气汤的化学成分及作用靶标基因,从comparative toxicogenomics database(CTD)数据库收集糖尿病胃轻瘫的靶标基因,将两者取交集后得到加味桃核承气汤--糖尿病胃轻瘫靶基因交集,运用STRING构建蛋白质间相互作用网络,并将结果进行网络可视化展示,通过Cytospace软件Clue GO,Clue Pedia插件进行加味桃核承气汤--糖尿病胃轻瘫靶基因交集的基因本体论(gene ontology,GO)分析和京都基因与基因组百科全书(KEGG)通路富集分析,并将结果进行可视化展示。最后利用CTD数据库并结合文献学习,获取交集基因于糖尿病胃轻瘫的疾病治疗作用。结果:加味桃核承气汤的621个靶点基因中有25个靶点与糖尿病胃轻瘫相互关联,该方可能通过影响MLNR,SST,PTGS1,HRH2,HTR3A,HTR4,HTR7,NOS3基因表达,改善胃肠激素水平,影响血清素与其受体结合,活化腺苷酸环化酶(adenylate cyclase,AC),诱导环磷酸腺苷(cyclic adenosine monophosphate,c AMP),蛋白激酶A(protein kinase A,PKA)表达,从而激活AC/c AMP/PKA信号通路,并调节Ca2+/K+通道的开放,控制离子平衡,继而促进胃平滑肌适应,收缩胃平滑肌以调节胃容量,同时改善胃酸分泌,保护胃黏膜,不排除改善血管收缩功能、血流动力学的可能。结论:网络药理学方法科学分析加味桃核承气汤通过多方面防治糖尿病胃轻瘫的作用机制,阐释其中医药多靶点、多通路防治糖尿病胃轻瘫的治疗优势,为加味桃核承气汤后续的实验研究提供研究方向和理论参考。

Mechanism of Modified Taohe Chengqitang in Treating Diabetic Gastroparesis Based on Network Pharmacology

Objective: To study the mechanism of modified Taohe Chengqitang in preventing and treating diabetic gastroparesis by regulating relative genes and signaling pathways based on network pharmacology. Method: Target genes of modified Taohe Chengqitang were obtained from Bioinformatics Analysis Tool for Molecular Mechanism of TCM (BATMAN-TCM) database, and target genes of diabetic gastroparesis were obtained from Comparative Toxicogenomics Database (CTD) database. The target genes of modified Taohe Chengqitang-diabetic gastroparesis intersection protein were obtained through the integration of two groups of genes. STRING was used to build the protein-protein interaction network and visualize the results. Cytospace software ClueGO, CluePedia plug-in were used for gene ontology (GO) analysis and enrichment analysis of KEGG pathway of modified Taohe Chengqitang-diabetic gastroparesis target genes intersection, and results were visualized. Finally, CTD database and literatures were used to obtain intersection genes in the treatment of diabetic gastroparesis. Result: Among 621 target genes in modified Taohe Chengqitang, 25 were related to diabetic gastroparesis. By regulating expressions of MLNR, SST, PTGS1, HRH2, HTR3A, HTR4, HTR7, NOS3 and other intersection genes, Taohe Chengqitang could improve the gastrointestinal hormone levels, affected the combination of serotonin and its receptors, activated adenylate cyclase (AC), and induced cyclic adenosine monophosphate (cAMP) and protein kinase A (PKA), so as to activiate AC/cAMP/PKA signaling pathway, regulate Ca²⁺/K⁺ channel, control ion balance, promote the adaptability of gastric smooth muscle, and contract gastric smooth muscle to regulate gastric volume. At the same time, gastric acid secretion was improved to protect gastric mucosa, which may help improve vasoconstriction and hemodynamics. Conclusion: Based on the network pharmacology, modified Taohe Chengqitang has multiple mechanisms in the prevention and treatment of diabetic gastroparesis. This study explored relevant signaling pathways, advantages and research directions of modified Taohe Chengqitang in treatment of diabetic gastroparesis.