基于网络药理学联合GEO芯片探讨肠安泻愈汤在肠易激综合征亚型中的分子机制

The Molecular Mechanism of Changan Xieyu Decoction in Irritable Bowel Syndrome Based on Network Pharmacology and GEO

目的采用网络药理学联合基因综合表达数据库(Gene Expression Omnibus,GEO)芯片差异分析探讨肠安泻愈汤治疗腹泻型与便秘型肠易激综合征的分子机制。方法采用R语言差异分析GEO芯片;检索TCMSP、PubChem数据库筛选肠安泻愈汤中柴胡、党参、枳实、茯苓、白术、白芍、紫菀、紫苏子、泽泻、薏苡仁10味中药的靶点;通过String、DAVID、TargetScan数据库对肠安泻愈汤治疗肠易激综合征(Irritable bowel syndrome,IBS)亚型的差异靶点进行PPI、GO、KEGG分析及miRNA预测。结果肠安泻愈汤可能通过山奈素、豆甾醇、槲皮素等多种有效成分,调控miR-34a-5p-MET、miR-429-PTGDR、miR-29a-HTR7与miR-205-5p-VEGFA、miR-199a-5p-IKBKB、miR-96-5p-MAP2K1等多组互作关系,调节HSP90AA1、VEGFA、IKBKB等蛋白互作,发挥蛋白激酶活性、蛋白质结合、ATP结合等分子功能,介导细胞凋亡、PI3K/Akt、miRNA等通路,调控细胞增殖、细胞自噬、氧化能量代谢与血管通透性、干扰素-γ、白三烯代谢等生命进程,治疗IBS-D与IBS-C亚型。结论本研究构建了肠安泻愈汤—IBS-D/IBS-C—靶点—miRNA互作网络,得出肠安泻愈治疗IBS-D、IBS-C亚型的分子机制。

Objective To investigate the molecular mechanism of Changan xieyu Decoction in the treatment of diarrhea-type and constipation-type irritable bowel syndrome using Gene Expression Omnibus(GEO)chip differential analysis of network pharmacology.Methods The GEO chip was analyzed by R language difference;the TCMSP and PubChem databases were searched to screen the 10 traditional Chinese medicines of Bupleurum,Codonopsis,Citrus aurantium,Poria,Atractylodes,Radix Paeoniae Rubra,Aster,Perilla Seed,Alisma,and Coix Seed.Targets of irritable bowel syndrome(IBS)subtypes in the treatment of Irritable bowel syndrome(IBS)were analyzed by PPI,GO,KEGG and miRNA prediction through String,DAVID,TargetScan database.Results Changan xieyu Decoction may regulate miR-34a-5p-MET,miR-429-PTGDR,miR-29a-HTR7 and miR-205-5p-through various active ingredients such as kaempferol,stigmasterol,and quercetin.VEGFA,miR-199a-5p-IKBKB,miR-96-5p-MAP2K1 and other groups of interactions,regulate HSP90AA1,VEGFA,IKBKB and other protein interactions,exert protein kinase activity,protein binding,ATP binding and other molecular functions,mediate Directs cell apoptosis,PI3K/Akt,miRNA and other pathways,regulates cell proliferation,cell autophagy,oxidative energy metabolism and vascular permeability,interferon-γ,leukotriene metabolism and other life processes,treats IBS-D and IBS-C subtype.Conclusion In this study,the Changanxieyu Decoction-IBS-D/IBS-C-target-miRNA interaction network was constructed,and the molecular mechanism of Changanxieyu s treatment of IBS-D and IBS-C subtypes was obtained.