基于网络药理学与分子对接技术的异钩藤碱抗肺纤维化的作用机制探究  

Exploring mechanism of isorhynchophylline in treatment of pulmonary fibrosis through network pharmacology and molecular docking

作　　者：边梦霓 杨征[2] 董永和[1] 邱敏[1] 高志祥 BIAN Mengni;YANG Zheng;DONG Yonghe;QIU Min;GAO Zhixiang(Department of Pharmacy,Baotou Medical College,Baotou 014040,China;Department of Cardiology,First Affiliated Hospital of Baotou Medical College,Baotou 014017,China)

机构地区：[1]包头医学院药学院,内蒙古包头014040 [2]包头医学院第一附属医院心内二科,内蒙古包头014017

出　　处：《药物评价研究》2022年第3期418-427,共10页Drug Evaluation Research

基　　金：国家自然科学基金资助项目(81160560);内蒙古自然科学基金项目(2011MS1131,2015MS0809,2019MS08061,2020MS08071,2020MS08077,2021MS08126);自治区大学生创新创业训练计划项目(S202119127007)。

摘　　要：目的 应用网络药理学与分子对接的方法阐明异钩藤碱抗肺纤维化的作用机制。方法 使用Swiss Target Prediction、DisGeNET等数据库预测异钩藤碱和肺纤维化的潜在靶点。通过拓扑分析筛选核心靶点,并对其进行基因本体论(GO)功能和京都基因和基因组百科全书(KEGG)通路富集分析。对筛选出的关键靶点进行分子对接实验验证结合活性。结果 靶点预测得到100个异钩藤碱和肺纤维化共同作用靶点,GO功能分析表明调节炎症反应、正向调节成纤维细胞增殖等多种生物过程参与肺损伤后的纤维化进程;得到了MAPK1、MAPK3、EGFR、VEGFA、PI3KCA、PI3KCD、AKT1、TNF等8个异钩藤碱治疗肺纤维化的预测靶点和以PI3K-Akt信号通路为主的潜在作用途径。分子对接结果表明异钩藤碱可以与选定的8个靶点进行结合。结论 异钩藤碱可以通过调节肺纤维化的某些生物过程,介导以PI3K-Akt信号通路为主的途径发挥肺损伤后的保护作用,为后续开展异钩藤碱抗肺纤维化的实验研究提供理论依据。Objective Application of network pharmacology and molecular docking to elucidate the mechanism of isorhynchophylline against pulmonary fibrosis.Methods The potential targets of isorhynchophylline and pulmonary fibrosis were first predicted through Swiss Target Prediction,DisGeNET,and other databases.Then the core targets were screened by topological analysis and subjected to Gene Ontology(GO) function and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analysis.Finally,molecular docking was performed to verify the binding activity.Results Target prediction yielded 100 predicted targets where isorhynchophylline and pulmonary fibrosis act together,and GO functional analysis indicated that multiple biological processes such as regulation of inflammatory response and positive regulation of fibroblast proliferation are involved in the fibrosis process after lung injury.Ultimately,MAPK1,MAPK3,EGFR,VEGFA,PI3KCA,PI3KCD,AKT1,TNF eight predicted targets of isorhynchophylline for the treatment of pulmonary fibrosis and a potential pathway based on the PI3K-Akt signaling pathway were identified.In addition,molecular docking results showed that isorhynchophylline could bind to the selected eight targets.Conclusion Isorhynchophylline may exert protective effects after lung injury by modulating certain biological processes of lung fibrosis and mediating a pathway dominated by the PI3 K-Akt signaling pathway,providing a theoretical basis for subsequent experiments on the anti-pulmonary fibrosis of isorhynchophylline.

关 键 词：异钩藤碱 肺纤维化 网络药理学 分子对接 作用机制 

分 类 号：R285.5[医药卫生—中药学]