基于网络药理学探讨健胃消胀片治疗胃肠动力障碍性疾病的作用机制

Discussion on the mechanism of Jianwei Xiaozhang tablets in treatment of gastrointestinal motility disorders based on network pharmacology

目的通过“化合物⁃靶标⁃通路⁃疾病”的网络药理研究模式,研究健胃消胀片在重症医学科治疗胃肠动力障碍性疾病(DGIM)的作用机制。方法通过中药系统药理学分析平台(TCMSP)筛选健胃消胀片的主要有效成分。TCMSP和Drug⁃Bank平台收集健胃消胀片主要有效成分的作用靶点。利用Genecards和在线人类孟德尔遗传(OMIM)数据库获取DGIM的相关靶点。通过Venny数据库获取药物成分和疾病靶点的交集靶点。采用Cytoscape 3.7.2软件构建健胃消胀片“化合物⁃交集靶点”网络图。利用STRING平台构建蛋白质⁃蛋白质相互作用(PPI)网络图。利用DAVID数据库对交集靶点进行GO功能富集分析和KEGG通路富集分析。结果通过TCMSP数据库共选取健胃消胀片候选化学物136个。通过TCMSP数据库和DrugBank数据库共得到2395个健胃消胀片的成分靶点。通过Genecards和OMIM数据库共得到1033个DGIM疾病靶点。维恩图分析显示健胃消胀片的成分靶点与DGIM的疾病靶点之间的交集靶点192个。“化合物⁃交集靶点”网络图显示,共有143个药物成分节点,183个靶节点。主要药物成分有β⁃谷甾醇、芒柄花黄素、异鼠李素等。PPI网络图显示共有191个节点,主要有羟色胺(HT)、胰岛素样生长因子(IGF)、白细胞介素(IL)等。GO功能富集分析共得到2623条条目。KEGG通路富集分析共得到174条相关通路。结论健胃消胀片通过参与糖代谢、信号转导、炎症反应等过程,调控肿瘤坏死因子(TNF)、白细胞介素⁃17(IL⁃17)、T辅助细胞17(Th17)细胞、缺氧诱导因子1(HIF1)、磷酸肌醇3激酶/丝氨酸/苏氨酸蛋白激酶(PI3K/Akt)等信号通路,发挥治疗胃肠动力障碍的作用。

Objective To study the mechanism of Jianwei Xiaozhang tablets in treatment of disorders of gastrointestinal motility(DGIM)in the Department of Critical Care Medicine,through the network pharmacological research mode of“compound⁃target⁃pathway disease”.Methods The main effective components of Jianwei Xiaozhang tablets were screened through the Traditional Chinese Medicine Systems Pharmacology Platform(TCMSP),and the effect targets of the main components of Jianwei Xiaozhang tablets were collected from TCMSP and DrugBank platforms.Corresponding effect targets of DGIM were obtained by using the Genecards and OMIM databases and the intersection targets of the drug components and disease targets were obtained by using the Venny database.The“compound intersection target”network diagram of Jianwei Xiaozhang tablets was plotted by using Cytascape 3.7.2 software.PPI network diagram was plotted by using STRING platform and GO function enrichment and KEGG pathway enrichment analyses concerning intersection targets were performed by using DAVID database.Results Through the TCMSP database,136 candidate chemicals for Jianwei Xiaozhang tablets were selected.A total of 2395 component targets of Jianwei Xiaozhang tablets were obtained through TCMSP database and DrugBank database.A total of 1033 DGIM disease targets were obtained through Genecards and OMIM databases.Venn diagram analysis showed that there were 192 set targets between the component targets of Jianwei Xiaozhang tablets and the disease targets of DGIM.“Compound intersection target”network diagram showed that there were 143 drug component nodes and 183 target nodes in total.The main pharmaceutical ingredients wereβ⁃Sitosterol,anthocyanin,isorhamnetin.The PPI network diagram showed a total of 191 nodes,mainly including serotonin(HT),insulin like growth factor(IGF),interleukin(IL).A total of 2623 entries were obtained through GO functional enrichment analysis.A total of 174 related pathways were obtained through enrichment analysis of KEGG pathways.Conclusion In treatment of DGIM,Jianwei Xiaozhang tablets might be involved in glucose metabolism,signal transduction and inflammatory reaction,and might be also involved in the regulation of tumor necrosis factor(TNF),IL⁃17,T⁃helper cell 17(Th17)cells,hypoxia inducible factor 1(HIF1),phosphoinositol 3 kinase/serine/threonine protein kinase(PI3K/Akt)and other signal pathways as well.