基于网络药理学和分子对接探究槐杞黄颗粒治疗IgA肾病的作用机制  

Mechanism of Huaiqihuang granules in the treatment of IgA nephropathy based on network pharmacology and molecular docking

作　　者：李倩[1] 王雨馨 刘识鉴 赵耀[2] 孔凡武[2] LI Qian;WANG Yu⁃xin;LIU Shi⁃jian;ZHAO Yao;KONG Fan⁃wu(Department of Nephrology,The First Affiliated Hospital of Shihezi University,Shihezi 832008,China;Department of Nephrology,The Second Affiliated Hospital of Harbin Medical University,Harbin 150081,China)

机构地区：[1]石河子大学第一附属医院肾病科,新疆石河子832008 [2]哈尔滨医科大学附属第二医院肾脏病学科,黑龙江哈尔滨150081

出　　处：《哈尔滨医科大学学报》2024年第5期462-471,共10页Journal of Harbin Medical University

基　　金：湖北陈孝平科技发展基金会2023年度免疫性疾病研究槐杞黄专项基金(CXPJJH123004-013)

摘　　要：目的 通过网络药理学及分子对接技术探讨槐杞黄颗粒(Huaiqihuang granules, HQH)治疗IgA肾病(IgA nephropathy, IgAN)的作用机制。方法 在中药系统药理数据库和分析平台(Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform, TCMSP)检索HQH的有效活性成分及相关靶点;在GeneCards、在线人类孟德尔遗传数据系统(Online Mendelian Inheritance in Man, OMIM)、DisGeNET数据库检索IgAN疾病靶点;利用维恩图对二者取交集;通过David数据库进行富集分析;在STRING平台构建蛋白互作(protein-protein interaction, PPI)网络;使用Cytoscape绘制HQH干预IgAN的疾病-通路-靶点-成分-药物网络图,利用CytoNCA的度中心性(degree centrality, DC)算法筛选出核心基因;最后利用AutoDock Tools软件探索分子与蛋白质之间的相互作用和结合模式,并用PyMOL可视化。结果 在TCMSP获取到黄精及枸杞子有效成分57个,作用靶点202个,在Pubmed及知网中检索到槐耳作用靶点73个;鉴定IgAN相关靶点199个;得到药物与疾病的交集靶点22个;其中槲皮素、β-谷甾醇、黄芩苷、豆甾醇为HQH核心成分;白细胞介素-6(interleukin-6,IL6)、肿瘤坏死因子(tumor necrosis factor, TNF)、白细胞介素-1β(interleukin-1beta, IL1β)、CXC基序趋化因子配体8(C-X-C motif chemokine ligand 8,CXCL8)、趋化因子2(C C motif ligand 2,CCL2)、γ-干扰素(interferon-γ,IFNG)、白细胞介素-10(interleukin-10,IL10)、细胞间黏附分子-1(intercellular cell adhesion molecule-1,ICAM1)、白细胞介素-2(interleukin-2,IL2)、C-反应蛋白(C-reactive protein, CRP)、转化生长因子β1(transforming growth factor beta1,TGFβ1)为HQH干预IgAN的核心靶点;涉及到的主要通路为细胞因子-细胞因子受体相互作用、糖尿病并发症中的糖基化终末产物(advanced glycation end products, AGE)-糖基化终末产物受体(receptor for advanced glycation end products, RAGE)信号通路(AGE-RAGE)信号通路、白细胞介素-17(interlObjective To elucidate the mechanism by which Huaiqihuang granules(HQH)treat IgA nephropathy(IgAN)through network pharmacology and molecular docking tech⁃niques.Methods Active ingredients and associated targets of HQH were identified using the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP).Targets related to IgAN were sourced from GeneCards,Online Mendelian Inheritance in Man(OMIM),and DisGeNET databases.The intersection of these two sets was determined using a Venn diagram.Enrichment analysis was conducted via the David database.A protein⁃protein interaction(PPI)network was constructed on the STRING platform;Cytoscape was employed to visualize the disease⁃pathway⁃target⁃drug network diagram illustrating HQH’s intervention in IgAN,with core genes identified using CytoNCA degree centrality(DC)algorithm.Finally,AutoDock Tools software facilitated exploration of molecular interactions and binding patterns between molecules and proteins,while PyMOL provided visualization capabilities.Results A total of 57 active components and 202 active targets were extracted from TCMSP,alongside 73 additional active targets retrieved from PubMed and CNKI.In total,199 IGAN⁃related targets were recognized,yielding 22 intersecting targets between drugs and diseases.Quercetin,β⁃si⁃tosterol,baicalin,and stigmasterol emerged as core components of HQH.Core intervention tar⁃gets for HQH in IgAN included interleukin⁃6(IL6),tumor necrosis factor(TNF),interleukin⁃1beta(IL1β),C⁃X⁃C motif chemokine ligand 8(CXCL8),C C motif ligand 2(CCL2),inter⁃feron⁃γ(IFNG),interleukin⁃10(IL10),intercellular cell adhesion molecule⁃1(ICAM1),in⁃terleukin⁃2(IL2),C⁃reactive protein(CRP),and transforming growth factor beta1(TGFβ1).Major pathways implicated include cytokine⁃cytokine receptor interactions;advanced glycation end products(AGE)⁃receptor for advanced glycation end products(RAGE)(AGE⁃RAGE)sig⁃naling in diabetes complications;interleukin⁃17(IL17)signaling;nucle

关 键 词：IGA肾病 网络药理学 分子对接 槐杞黄颗粒 

分 类 号：R285.5[医药卫生—中药学]