基于网络药理学和分子对接技术研究安神定志方 干预创伤后应激障碍焦虑样行为的机制

Mechanism of Anshen Dingzhi Prescription Intervening Against Anxiety-like Behavior in Post-traumatic Stress Disorder:An Analysis Based on Network Pharmacologyand Molecular Docking

目的采用网络药理学方法和分子对接技术探讨安神定志方(Anshen Dingzhi Prescription,ADP)干预创伤后应激障碍(post-traumatic stress disorder,PTSD)的作用机制。方法使用TCMSP、TCMID等筛选ADP的有效成分及靶点,借助TTD和GeneCards等数据库收集PTSD靶点;将ADP成分靶点与PTSD疾病靶点取交集靶点;通过STRING数据库构建靶点互作网络筛选核心靶点;对交集靶点进行GO功能分析和KEGG富集分析,构建“中药—成分—靶点—通路”网络;选取疾病关键靶点与ADP主要活性成分进行分子对接,并开展动物实验验证。结果ADP防治PTSD的网络中共有145个活性成分、188个交集靶点、75个关键靶点、238个生物过程、54个细胞组分、62个分子功能。对PTGS2、ESR1、MAPK14与ADP关键活性成分进行分子对接,结果显示具有较好的结合活性。在动物实验中,与正常对照组比较,ADP可明显改善PTSD的焦虑样行为与突触功能,同时增加AKT/mTOR蛋白的表达水平。结论ADP治疗PTSD可能通过调控AKT/mTOR信号通路影响突触能传递、钙信号转导、蛋白合成等发挥作用。

Objective To investigate the mechanism of action of Anshen Dingzhi Prescription(ADP)in intervening against post-traumatic stress disorder(PTSD)based on network pharmacology and molecular docking.Methods The data bases including TCMSP and TCMID were used to screen out the effective constituents and targets of ADP,and TTD and GeneCards databases were used to collect PTSD-related targets.Intersecting targets were obtained for the targets of ADP constituents and the targets of PTSD.STRING data base was used to construct a protein-protein interaction network for the targets to screen out core targets.Gene ontology(GO)enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis were performed for the intersecting targets,and a traditional Chinese medicine-constituent-target-pathway network was constructed.Finally,molecular docking was performed for the key targets of PTSD and the main active components of ADP,and animal experiments were conducted for validation.Results In the network of the prevention and treatment of PTSD by ADP,there were 145 active components,188 intersecting targets,75 key targets,238 biological processes,54 cellular components,and 62 molecular functions.Molecular docking showed good binding activity between PCGS2/ESR1/MAPK14 and the key active components of ADP.Animal experiments showed that compared with the normal control group,ADP significantly improved anxiety-like behaviors and synaptic function in PTSD and increased the expression of AKT/mTOR proteins.Conclusion ADP exerts a therapeutic effect on PTSD possibly by regulating the AKT/mTOR signaling pathway to affect synaptic energy transmission,calcium signal transduction,and protein synthesis.