中国药学(英文版) ›› 2021, Vol. 30 ›› Issue (7): 556-569.DOI: 10.5246/jcps.2021.07.044
李成1, 朱玉华1, 孙晓旻1, 许静1, 熊丹1, 王娟1, 高新庐1, 陈绪龙1,2,*()
收稿日期:
2021-02-16
修回日期:
2021-04-15
接受日期:
2021-04-25
出版日期:
2021-07-27
发布日期:
2021-07-27
通讯作者:
陈绪龙
作者简介:
基金资助:
Cheng Li1, Yuhua Zhu1, Xiaomin Sun1, Jing Xu1, Dan Xiong1, Juan Wang1, Xinlu Gao1, Xulong Chen1,2,*()
Received:
2021-02-16
Revised:
2021-04-15
Accepted:
2021-04-25
Online:
2021-07-27
Published:
2021-07-27
Contact:
Xulong Chen
摘要:
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DisGeNET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 (Gene ontology)功能、KEGG (Kyoto encyclopedia of genes and 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。
Supporting:
李成, 朱玉华, 孙晓旻, 许静, 熊丹, 王娟, 高新庐, 陈绪龙. 基于网络药理学和分子对接技术探讨雷公藤致急性肾损伤的多重作用机制[J]. 中国药学(英文版), 2021, 30(7): 556-569.
Cheng Li, Yuhua Zhu, Xiaomin Sun, Jing Xu, Dan Xiong, Juan Wang, Xinlu Gao, Xulong Chen. The multiple mechanisms of tripterygium wilfordii-induced acute kidney injury based on network pharmacology and molecular docking[J]. Journal of Chinese Pharmaceutical Sciences, 2021, 30(7): 556-569.
Figure 4. TW inducing AKI "disease-component-target-pathway" network diagram. The red square is the disease, the green circle is the target genes, the blue arrow is the chemical component, the pink triangle is the pathway, and the line represents each side, indicating the interaction between each other.
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