摘要
Acute kidney injury(AKI)is a common and serious health issue with a growing incidence and mortality rate.Tripterygium wilfordii(TW)is a traditional Chinese medicine that has been reported to cause kidney damage.However,the associated mechanism of TW-induced AKI remains unclear.Therefore,we aimed to uncover the associated mechanisms of AKI induced by TW using network pharmacology and bioinformatics.The candidate compounds of TW and the potential targets were screened using TCMSP and CTD database,and the AKI-related targets were identified from the Dis Ge NET database.The disease targets were intersected with the drug targets,and the Wayne diagram was drawn by Venny 2.1.0 software.We developed proteinprotein interactions(PPI)network and the“disease-compound-target-pathway”network through the Cytoscape software.By using the DAVID database,GO and KEGG enrichment analysis was carried out to reveal the potential signaling pathways of the compound-TW-induced AKI.Meanwhile,the Auto dock vina 1.1.2 was used for molecular docking to verify the active compound and key targets’binding ability.Critical compounds and key targets of TW-induced AKI were identified,including triptolide,kaempferol,β-sitosterol,nobiletin,stigmasterol,TNF,and so on.The GO analysis showed that potential genes’biological function was mainly involved in apoptosis,oxidative stress,and inflammation.Moreover,eight signaling pathways were found,including the HIF-1 signaling pathway,VEGF signaling pathway,apoptosis,and so on.The molecular docking results proved that the core compound’s affinity with the corresponding protein of the gene targets was good.This study preliminarily predicted the core toxic compounds,targets,and related pathways of TW-induced AKI,providing a theoretical basis for the follow-up clinical rational drug use and related research work of TW.
急性肾损伤(Acute kidney injury,AKI)是一个严重的健康问题,发病率和死亡率都在增加。雷公藤(Tripterygium wilfordii,TW)是一种传统的中药,已被报道可引起肾脏损伤。然而,TW诱导AKI的相关机制尚不清楚。因此,本研究旨在利用网络药理学和生物信息学技术揭示TW诱导AKI的相关机制。利用TCMSP和CTD数据库对TW的候选化合物和潜在靶标进行筛选,通过Dis Ge NET获取AKI相关靶标基因,取两靶点交集获取雷公藤致AKI的潜在作用靶点。借助STRING数据库软件绘制蛋白相互作用网络(Protein-protein interaction,PPI),使用Cytoscape3.8.0软件构建"疾病-靶点-成分-通路"网络图,采用DAVID生物信息数据库对交集靶点进行GO(Geneontology)功能、KEGG(Kyoto encyclopedia of genesand genomes)通路的富集分析。最后利用vina1.1.2进行分子对接,验证了活性化合物和关键靶点的结合能力。文章确定了TW诱导AKI的关键化合物和关键靶点,包括雷公藤甲素、山奈酚、β谷甾醇、蜜桔黄素、豆甾醇、TNF等。GO富集分析显示雷公藤诱导AKI主要涉及细胞凋亡、氧化应激及炎症反应等生物过程。此外,还发现了8条相关的信号通路,包括HIF-1信号通路、VEGF信号通路、凋亡通路等。分子对接结果表明,核心化合物与基因靶点相应蛋白的亲和力较好。本文从网络药理学的角度初步预测了TW诱导AKI的核心毒性化合物,靶点及相关途径,为TW后续临床合理用药及相关研究工作提供理论依据。
基金
The Science Foundation of Health and Family Planning Commission of Jiangxi Province(Grant No.20181140)
the Science and Technology Research Project of Jiangxi Provincial Department of Education(Grant No.GJJ201819,180919)。
