基于GEO基因芯片结合网络药理学和分子对接技术探究火把花根片治疗IgA肾病的作用机制

Mechanism of Huobahuagen Tablet in the treatment of IgA nephropathy based on GEO gene chip,network pharmacology and molecular docking technology

目的基于GEO基因芯片及网络药理学和分子对接技术探究火把花根片(HBHGT)治疗IgA肾病(IgA nephropathy,IgAN)的作用机制。方法从DrugBank、OMIM、GeneCards3个疾病数据库结合GEO基因芯片获得IgAN的疾病靶点。从中药系统药理学数据库与分析平台(traditional Chinese medicine systems pharmacology database and analysis platform,TCMSP)、本草组鉴、BATMAN-TCM 3个中药数据库、相关文献以及SwissTargetPrediction数据库获得HBHGT的主要成分和靶点。对HBHGT-IgAN交集利用STRING构建蛋白互作(protein-protein interaction,PPI)网络,筛选出关键靶点。进行基因本体(gene ontology,GO)注释和京都基因与基因组百科全书(Kyoto encyclopedia of genes and genomes,KEGG)富集分析后对关键成分及关键靶点进行分子对接验证。结果HBHGT治疗IgAN的核心成分为雷公藤红素、雷公藤甲素等,核心靶点有白细胞介素-6(interleukin-6,IL-6)、纤维连接蛋白1(fibronectin1,FN1)、白蛋白(albumin,ALB)等,分子对接显示大部分靶点与成分有着较好的结合活性。HBHGT治疗IgAN通路主要有核因子-κB(nuclear factor-κB,NF-κB)、磷脂酰肌醇3-激酶(phosphoinositide 3-kinase,PI3K)/蛋白激酶B(protein kinase B,Akt)、肿瘤坏死因子(tumor necrosis factor,TNF)等信号通路。结论火把花根片可通过多靶点、多通路来介导免疫和炎症反应,修复血管损伤,改善肾脏炎症,减少蛋白尿及血尿,延缓IgAN的进展,以达到治疗IgAN的效果。

Objective To explore the mechanism of Huobahuagen Tablet(HBHGT)in the treatment of IgA nephropathy(IgAN)based on GEO gene chip,network pharmacology and molecular docking technology.Methods The disease targets of IgAN were obtained from three disease databases such as DrugBank,OMIM and GeneCards combined with GEO gene chip.The main components and targets of HBHGT were obtained from three traditional Chinese medicine databases such as traditional Chinese medicine systems pharmacology database and analysis platform(TCMSP),HERB,BATMAN-TCM and relevant literature and SwissTargetPrediction database.For the HBHGT-IgAN intersection,the protein-protein interaction(PPI)network was constructed by STRING to screen the key targets.After gene ontology(GO)and Kyoto encyclopedia of genes and genomes(KEGG)enrichment analysis,the key components and key targets were verified by molecular docking.Results The core components of HBHGT in the treatment of IgAN were triptolide,celastrol,triptonide,etc.The core targets included interleukin-6(IL6),fibronectin1(FN1),albumin(ALB),etc.Molecular docking showed that most of the targets had good binding activity with the components.The main pathways of IgAN treated by HBHGT were nuclear factor-κB(NF-κB),phosphoinositide 3-kinase(PI3K)/protein kinase B(Akt),tumor necrosis factor(TNF)signaling pathways and other signaling pathways.Conclusion HBHGT can mediate immune and inflammatory reactions through multiple targets and channels,repair vascular injury,improve renal inflammation,reduce proteinuria and hematuria,and delay the progress of IgAN,so as to achieve the effect of treating IgAN.