基于网络药理学探讨麻杏石甘汤治疗急性肺损伤的机制  

The mechanism of Maxing Shigan Decoction in the treatment of acute lung injury based on network pharmacology

作　　者：程赛 陈伟[2] 吴钢伟[3] 张淑玫 张旗 CHENG Sai;CHEN Wei;WU Gangwei;ZHANG Shumei;ZHANG Qi(Department of Natural Pharmacology,School of Pharmacy,Fujian Medical University,Fuzhou 350122,China;Department of Pharmaceutical Analysis,School of Pharmacy,Fujian Medical University,Fuzhou 350122,China;Department of Pharmacy,Fujian Provincial Hospital,Fuzhou 350001,China)

机构地区：[1]福建医科大学药学院天然药物学系,福州350122 [2]福建医科大学药学院药物分析系,福州350122 [3]福建省立医院药学部,福州350001

出　　处：《西北药学杂志》2022年第1期51-58,共8页Northwest Pharmaceutical Journal

基　　金：国家自然科学基金项目(编号:81173562);福建医科大学高层次人才科研启动经费项目(编号:XRCZX2017030)。

摘　　要：目的借助网络药理学的方法研究麻杏石甘汤(MXSGD)的主要成分及其相应的靶点和对应的通路,预测MXSGD治疗急性肺损伤(acute lung injury,ALI)的作用机制。方法首先在TCMSP数据库中检索MXSGD的成分和靶点。用Cytoscape绘制药物有效成分及其相应靶点相互关联的网络图。在GeneCard数据库中检索ALI的疾病靶点,将药物与疾病的靶点信息在韦恩图中得到两者共有的部分,最后将两者共有的部分在DAVID数据库中进行gene ontology(GO)富集分析和Kyoto encyclopedia of genes and genomes(KEGG)通路分析。为了进一步探明MXSGD对ALI的作用,建立了大鼠ALI模型,并进行了肺组织切片观察、炎症因子检测和Western blot检测。结果预测出MXSGD有134种成分以及1742个基因,急性肺损伤的治疗靶点有1701个,将两者取交集得到潜在靶点136个。DAVAD结果表明,MXSGD治疗ALI的关键靶点主要参与乙型肝炎通路、TNF信号通路、甲型流感通路、HIF-1信号通路、Toll样受体信号通路、T细胞受体信号通路、PI3K-Akt信号通路和甲状腺激素信号通路等。MXSGD能够降低ALI大鼠体内炎症因子的含量,减轻肺部损伤的严重性。Western blot实验结果显示,MXSGD可以上调PI3K\\AKT蛋白的表达。结论借助网络药理学揭示了MXSGD是通过多种成分、多个靶点和多条通路相互作用的机制治疗ALI。Objective To explore the effective ingredients,targets and pathways of Maxing Shigan Decoction(MXSGD)through the method of network pharmacology,and to explain the mechanism of its treatment of acute lung injury(ALI).Methods The components of MXSGD and its targets were searched through TCMSP database and literature review,and the component-target network diagram was constructed with Cytoscape software.The targets of ALI were obtained by using the Gene Card database,then Venn diagram was used to obtain the intersection targets between the drug targets and the disease targets,and Cytoscape was used to construct the component-intersection target-disease network diagram,and finally the DAVID database was used to compare the intersection target for gene ontology(GO)enrichment and Kyoto encyclopedia of genes and genomes(KEGG)pathway analysis.The ALI model of rats was established,and lung tissue sections,inflammatory factors detection and Western blot protein expression experiments were performed to verify the therapeutic effect of MXSGD on ALI.Results It is predicted that MXSGD has 134 components and 1742 genes,1701 therapeutic targets for ALI,and a total of 136 potential targets from the intersection.DAVAD enrichment analysis showed the key targets of MXSGD in the treatment of ALI are mainly involved in hepatitis B,TNF,influenza A,HIF-1,Toll-like receptors,NOD-like pathway,T cell receptor,PI3K-Akt,thyroid hormone signaling pathways and other important pathways.Pharmacodynamic experiments showed MXSGD could significantly reduce the content of inflammatory factors and the degree of lung injury in ALI rats.Western blot assay showed MXSGD could significantly up-regulate the expression of PI3K\\Akt protein.Conclusion This study preliminarily revealed MXSGD from the perspective of network pharmacology.The mechanism of action of multiple components,multiple targets and multiple pathways in the treatment of ALI provides reference for the study of the mechanism of action of TCM compounds.

关 键 词：麻杏石甘汤 急性肺损伤 网络药理学 通路 靶点 

分 类 号：R285.5[医药卫生—中药学]