基于网络药理学的甲泼尼龙治疗腹膜纤维化作用机制研究

Mechanism of Methylprednisolone in the Treatment of Peritoneal Fibrosis Based on Network Pharmacology

目的探讨甲泼尼龙(MP)多靶点、多途径治疗腹膜纤维化(PF)的作用机制。方法采用计算机检索PubChem,Swiss Target Prediction等数据库中有关MP的作用靶点,并利用GeneCards及OMIM等数据库筛选PF的靶点基因,绘制Venn图,确定MP和PF的共同靶点基因,采用Cytoscape构建化学成分-疾病-作用靶点相互作用网络,并采用R软件进行GO功能注释和KEGG通路富集分析。结果共收集100个MP作用靶点,预测2 104个PF疾病靶点;其中,MP有65个潜在靶点可治疗PF,包括白细胞介素6(IL-6)、丝裂原活化蛋白激酶3(MAPK3)、丝裂原活化蛋白激酶1(MAPK1)、表皮生长因子受体(EGFR)、哺乳动物雷帕霉素靶蛋白(mTOR)、丝裂原活化蛋白激酶14(MAPK14)等。通过GO功能富集筛选出19条分析信息;通过KEGG通路富集分析确定了7条作用通路,如蛋白丝氨酸/苏氨酸激酶活性、蛋白酪氨酸激酶活性、MAPK信号通路及EGFR信号通路等。结论 MP可能具有抗PF作用,其作用机制与IL-6,m TOR,EGFR,MAPK通路等相关。

Objective To investigate the mechanism of methylprednisolone(MP)in the multi-target and multi-channel treatment of peritoneal fibrosis(PF).Methods The potential targets of MP were collected from PubChem,Swiss Target Prediction and other databases,and the target genes of PF were screened by GeneCards,OMIM and other databases.Then the common target genes of MP and PF were verified by creating a Venn diagram,and the protein-protein interaction(PPI)network of ingredient-disease-target was established via Cytoscape.Besides,GO function enrichment analysis and KEGG pathway enrichment analysis were implemented by R software.Results A total 100 MP targets were collected and 2104 PF disease targets were predicted.Among them,MP has 65 potential targets that could treat PF,including interleukin-6(IL-6),mitogen-activated protein kinase 3(MAPK3),mitogen-activated protein kinase 1(MAPK1),epidermal growth factor receptor(EGFR),mammalian target of rapamycin(mTOR),mitogen-activated protein kinase 14(MAPK14)and so on.A total of 19 items of analysis information were screened by GO function enrichment analysis.Seven pathways were identified by KEGG pathway enrichment analysis,such as protein serine/threonine kinase activity,protein tyrosine kinase activity,MAPK signaling pathway and EGFR signaling pathway.Conclusion MP may have an effect on PF,and its mechanism is related to IL-6,mTOR,EGFR and MAPK pathways.