基于网络药理学和分子对接探讨丹酚酸B防治皮瓣缺血再灌注损伤的作用机制  

Analysis of the mechanism of the treatment of flap ischemia/reperfusion injury with salvianolic acid B based on network pharmacology and molecular docking

作　　者：冶品陶 刘勇 YE Pintao;LIU Yong(Graduate School,Hunan University of Chinese Medicine,Hunan Province,Changsha410000,China;Department of Hand and Foot Microsurgery,Changde Hospital Affiliated to Hunan University of Chinese Medicine,Hunan Province,Changde415000,China)

机构地区：[1]湖南中医药大学研究生院,湖南长沙410000 [2]湖南中医药大学附属常德医院手足显微外科,湖南常德415000

出　　处：《中国当代医药》2023年第35期16-20,F0003,共6页China Modern Medicine

摘　　要：目的基于网络药理学和分子对接探讨丹酚酸B治疗对皮瓣缺血再灌注(I/R)损伤的作用机制。方法依托swiss target predictiont、SuperPred数据库筛选丹酚酸B的作用靶点,并结合Uniprot数据库筛选药物有效靶点。利用GeneCards、TTD、OMIM数据库检索与皮瓣I/R相关靶点,进而获得丹酚酸B和皮瓣I/R的交集靶点,将药物-交集基因上传至相互作用数据库String进行蛋白相互作用网络构建(PPI),通过David数据库对丹酚酸B防治皮瓣I/R的潜在靶点进行GO和KEGG通路富集分析,将筛选得到的核心靶点运用CB dock对关键靶点与相应活性成分进行分子对接验证。结果筛选得到丹酚酸B治疗皮瓣I/R的潜在靶点39个,其中JUN、CASP3、MMP9、APP、MAPK1、MTOR、NFKB1为核心靶点。GO功能富集分析得到生物过程、细胞组成、分子功能条目分别为91、28、24条;KEGG通路富集分析发现丹酚酸B防治皮瓣I/R主要相关的通路有脂质与动脉粥样硬化、白介素-17信号通路、肿瘤坏死因子信号通路、动脉粥样硬化与流体剪应力等。活性成分与核心靶点的分子对接结果表明,丹酚酸B的活性成分与自由值大于15的3个核心靶点之间具有良好的结合亲和力和相互作用模式。结论丹酚酸B通过多靶点、多途径的作用方式,从激活细胞自噬来促进血管新生、抑制细胞凋亡与氧化应激反应、减轻炎症因子的合成和分泌等方面发挥防治皮瓣I/R的作用,为后续研究中药单体调控“细胞自噬”深入研究提供理论基础。Objective To explore the mechanism of salvianolic acid B in the treatment of flap ischemia/reperfusion(I/R)injury based on network pharmacology and molecular docking.Methods The action targets of salvianolic acid B were screened based on swiss target predictiont and SuperPred database,and the effective drug targets were screened in combination with Uniprot database.GeneCards,TTD and OMIM databases were used to search the targets related to flap I/R,and then the intersection targets of salvianolic acid B and flap I/R were obtained,and the drug-intersection genes were uploaded to the interaction database String for protein-protein interaction networks(PPI).The GO and KEGG pathway enrichment analysis of potential targets of salvianolic acid B for preventing I/R in skin flaps was carried out through the David database.The selected core targets were used to conduct molecular docking verification between key targets and corresponding active ingredients by using CB dock.Results A total of 39 potential targets of salvianolic acid B for the treatment of flap I/R were screened,of which JUN,CASP3,MMP9,APP,MAPK1,MTOR and NFKB1 were the core targets.GO functional enrichment analysis of biological process,cell composition and molecular function entries were 91,28,24 respectively,KEGG pathway enrichment analysis found that the main pathways related to the prevention and treatment of flap I/R:lipid and atherosclerosis,interleukin-17 signaling pathway,and tumor necrosis factor signaling pathway,atherosclerosis and fluid shear stress.The molecular docking results of the active ingredient and the core target showed that the active ingredient of salvianolic B had a good binding affinity and interaction mode between the three core targets with a free value greater than 15.Conclusion Salvianolic acid B plays the role of preventing and treating flap I/R from activating cell autophagy to promote angiogenesis,inhibiting cell apoptosis and oxidative stress response,and reducing the synthesis and secretion of inflammatory factors,providing

关 键 词：网络药理学 分子对接 丹酚酸B 皮瓣缺血再灌注损伤 靶点预测 

分 类 号：R363[医药卫生—病理学]