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基于网络药理学和分子对接技术探索贝特类药物在缺血性脑卒中治疗中调节缺氧诱导因子-1α(HIF-1α)的机制

Exploring the mechanism of fibrates regulating HIF-1A in the treatment of ischemic stroke based on network pharmacology and molecular docking.

作者信息

Yang Fengjiao, Yang Zixuan, Yan Ya, Gu Yun, Wang Pengyu, Wang Min, Chen Jianjie, Du Xiaoshan, Wang Guangming

机构信息

College of Clinical Medicine, Dali University, Dali, 671000, Yunnan, People's Republic of China.

Department of Pharmacy, The People's Hospital of Baoshan, Baoshan, 678000, Yunnan, People's Republic of China.

出版信息

BMC Res Notes. 2024 Dec 26;17(1):387. doi: 10.1186/s13104-024-07031-z.

Abstract

Fibrates can prevent and treat ischemic stroke (IS), the occurrence and development of IS is closely related to hypoxia-inducible factor-1A (HIF-1A). However, the exact mechanism by which fibrates regulate HIF-1A to treat IS remains unclear. So network pharmacology and molecular docking were used to explore the mechanism by which fibrates regulate HIF-1A to treat IS, firstly, the structure of five fibrates were obtained by reviewing the literature and pharmacopoeia, then the potential targets of fibrates, IS, HIF1A and HIF1A-related genes were obtained through various databases, their common targets were obtained through Venny 2.1.0. The PPI network diagram of fibrates, IS and HIF1A-related genes was plotted by String and Cytoscape3.8.1. The GO functional analysis results and KEGG pathways of fibrates, IS, HIF1A and HIF1A related genes were obtained by Metascape. Finally, the molecular docking of fibrates and HIF1A was performed by AutoDock. The common targets of five fibrates and IS showed that only 3 fibrates contained HIF1A, GO functional analysis, KEGG pathway analysis and molecular docking showed that fibrates can better regulate HIF1A to treat IS, its main action pathways are pathways in cancer, lipid and atherosclerosis and HIF-1 signaling pathway.

摘要

贝特类药物可预防和治疗缺血性中风(IS),IS的发生和发展与缺氧诱导因子-1A(HIF-1A)密切相关。然而,贝特类药物调节HIF-1A治疗IS的确切机制仍不清楚。因此,采用网络药理学和分子对接方法探讨贝特类药物调节HIF-1A治疗IS的机制,首先通过查阅文献和药典获得5种贝特类药物的结构,然后通过各种数据库获得贝特类药物、IS、HIF1A及HIF1A相关基因的潜在靶点,通过Venny 2.1.0获得它们的共同靶点。利用String和Cytoscape3.8.1绘制贝特类药物、IS及HIF1A相关基因的PPI网络图。通过Metascape获得贝特类药物、IS、HIF1A及HIF1A相关基因的GO功能分析结果和KEGG通路。最后,通过AutoDock对贝特类药物和HIF1A进行分子对接。5种贝特类药物与IS的共同靶点显示,只有3种贝特类药物含有HIF1A,GO功能分析、KEGG通路分析和分子对接显示,贝特类药物可更好地调节HIF1A治疗IS,其主要作用途径为癌症、脂质与动脉粥样硬化通路以及HIF-1信号通路。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7c5d/11670374/545070aa473a/13104_2024_7031_Fig1_HTML.jpg

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