基于网络药理学探讨消痔灵治疗直肠黏膜内脱垂的作用机制  

Mechanism of Xiaozhiling in Treatment of Internal Rectal Prolapse Based on Network Pharmacology

作　　者：柯敏辉[1] 李雪玉[1] KE Minhui;LI Xueyu(Department of Anorectal Medicine,Second People's Hospital Affiliated to Fujian University of Traditional Chinese Medicine,Fuzhou 350003,China)

机构地区：[1]福建中医药大学附属第二人民医院肛肠科,福建福州350003

出　　处：《基层中医药》2022年第1期49-56,共8页Basic Traditional Chinese Medicine

基　　金：国家自然基金面上项目(81774118);福建省科技厅引导性项目(2019Y0029);福建中医药大学校管课题(X2019063-学科)。

摘　　要：目的运用网络药理学方法探讨消痔灵治疗直肠黏膜内脱垂(IRP)的可能作用机制。方法根据TCM-ID检索五倍子的主要成分,在CTD平台预测五倍子的3种主要成分与明矾的潜在靶点,使用GeneCards数据库挖掘IRP相关靶点,将收集到成分与疾病的靶点经交集得到共同靶点。通过STRING平台构建蛋白-蛋白相互作用网络,并利用Cytoscape 3.8.2软件筛选核心基因.3运用Metascape数据库对共同托点进行基因本体(Gene Ontology,GO)功能和京都基因与基因组百科全书(Kyoto Encyclopedia ofGenes and Genomes,KEGG)通路富集分析,通过Bioinformatics平台进行可视化处理:结果检索出药物靶点273个,疾病靶点935个,其中共同靶点98个,核心靶点有丝氨酸/苏氨酸蛋白激酶1(AKT1)、血管内皮生长因子A(VEGFA)、丝裂原活化蛋白激酶1(MAPK1)、转录因子AP-1(JUN)、白细胞介素-6(IL-6)等20位。GO分析结果显示主要富集于凋亡信号通路、细胞对化学应激的反应、对无机物的反应、细胞粘附调节等生物过程;其分子功能主要有细胞因子受体结合与活性、信号受体调节活性、细胞粘附分子结合等;细胞组分显示靶点多位于胞内囊腔区、血小板a颗粒及腔内、细胞外基质等;KEGG通路主要涉及磷脂酰肌醇-3-激酶-蛋白激酶B(PI3K-Akt)、丝裂原活化蛋白激酶(MAPK)、肿瘤坏死因子(TNF)、缺氧诱导因子-1(HIF-1)、叉头转录因子(FOXO)和白细胞介素-17(IL-17)信号通路等。结论消痔灵可能通过AKT1、VEGFA、MAPK1、JUN、IL-6等核心基因作用于PI3K-Akt、MAPK、TNF、HIF-1、FOXO和IL-17等关键通路,参与调控炎症反应及成纤维细胞生物学过程,从而起到治疗IRP的作用。Objective To explore the underlying mechanism of Xiaozhiling in the treatment of internal rectal prolapse(IRP)based on network pharmacology.Methods The main components of Galla Chinensis were retrieved according to TCM-ID.The potential targets of three main components of Galla Chinensis and Alumen were predicted on the CTD platform.The IRP-related targets were mined from GeneCards,and the common targets of components and the disease were obtained.The protein-protein interaction(PPI)network was constructed by STRING,and the core genes were screened out by Cytoscape 3.8.2.Gene Ontology(GO)function and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analyses of common targets were carried out by using Metascape,followed by visualization by the Bioinformatics platform.Results A total of 273 drug targets and 935 disease targets were obtained,including 98 common ones.The core targets were serine/threonine-protein kinase 1(AKT1),vascular endothelial growth factor A(VEGFA),mitogen-activated protein kinase 1(MAPK1),AP-1 transcription factor(JUN),interleukin-6(IL-6),etc.GO analysis showed that it was mainly enriched in biological processes such as apoptosis signaling pathway,cell responses to chemical stress and inorganic substances,and cell adhesion regulation,molecular functions such as cytokine receptor binding and activity,signal receptor regulatory activity,and cell adhesion molecule binding,and cellular components,such as intracellular vesicle lumen,platelet a granule and lumen,and extracellular matrix.KEGG pathways mainly involved phosphoinositide 3-kinase(PI3K)-Akt,MAPK,tumor necrosis factor(TNF),hypoxia-inducible factor 1(HIF-1),forkhead transcription factor(FOXO),and IL-17 signaling pathways.Conclusion Xiaozhiiing may act on key pathways such as PI3K-Akt,MAPK,TNF,HIF-1,FOXO,and IL-17 through core genes such as AKT1,VEGFA,MAPK1,JUN,and IL-6,and participate in the regulation of inflammatory response and fibroblast biological process to play a role in the treatment of IRP.

关 键 词：消痔灵 直肠黏膜内脱垂 网络药理学 炎症反应 成纤维细胞 

分 类 号：R73[医药卫生—肿瘤]