丹参-牛膝药对治疗骨质增生的作用机制研究

Exploration of the molecula mechanism of“Salvia miltiorrhiza-Achyranthesbidentata”in the treatment of bone hyperplasia

基于网络药理学及分子对接技术预测丹参-牛膝药对治疗骨质增生(Bone hyperplasia)的活性成分及相关的分子机制.利用中药系统药理学数据库与分析平台数据库(TCMSP)及BATMAN-TCM数据库平台筛选丹参-牛膝药对活性成分及作用靶点;利用OMIM、Genecard数据库搜索骨质增生疾病的相关靶点,取其与丹参-牛膝药对中化合物的作用靶点交集得到治疗骨质增生的潜在作用靶点.运用Cytoscape软件建立并分析有效化合物-作用靶点网络;利用String数据库平台分析作用靶点PPI网络;利用“clusterProfiler”软件包对作用靶点进行基因本体论(GO)功能和京都基因与基因组百科全书(KEGG)通路富集分析;利用Autodock-Vina模块将药对中核心化合物及核心靶点进行分子对接,以探索丹参-牛膝药对治疗骨质增生的作用机制.筛选得到丹参-牛膝药对中75个潜在的药效成分,协同作用于HSP90AA1、TP53、MAPK1、AKT1、JUN、STAT3、RELA、ESR1、FOS、MAPK14等180个靶点发挥治疗骨质增生的功效.分子对接结果显示,关键活性成分与核心靶点均能极好的结合.本研究从网络药理学的角度预测丹参-牛膝药对治疗骨质增生的潜在药效成分、作用靶点及作用机制,为丹参-牛膝药对临床用于骨质增生的治疗及其作用机制研究提供参考.

The study is to calculate the active ingredients and the related molecular mechanisms of“Salvia miltiorrhiza-Achyranthes bidentata”in the treatment of bone hyperplasia by network pharmacology and molecular docking method.TCMSP and BATMAN-TCM was used to search the active ingredients and related targets of“Salvia miltiorrhiza-Achyranthes bidentata”.OMIM and Genecard was used to search the related targets of Bone hyperplasia,potential targets for disease drugs were obtained.Cytoscape software was used to establish and analyze the effective compound-target network.String software was used to analyze the PPI network.The cluster Profiler was used to analyze the KEGG pathway and GO biological process.AutoDock software was used to verify the binding ability of active ingredients to key targets by molecular docking,so as to explore the mechanism of action of“Salvia miltiorrhiza-Achyranthes bidentata”drugs in the treatment of hyperosteogeny.75 effective components were screened out,which acted on synergically 180 targets such as MAPK1,AKT1,JUN,STAT3,RELA,ESR1,FOS and MAPK14 to play a therapeutic effect on hyperosteogeny.The result of molecular docking method showed that they were combined well between the key active ingredients and the core target spontaneously.This study reveals the basic pharmacological effects,targets and related mechanisms of“Salvia miltiorrhiza-Achyranthes bidentata”in treating bone hyperplasia were explored based on network pharmacology,which provided some theoretical support for later clinical and basic researches.