自拟出血性中风1号方治疗脑出血作用靶点的筛选及其生物学功能分析

Screening targets of self-designed Zhongfeng1 prescription in treatment of cerebral hemorrhage and their biological functions

目的筛选自拟出血性中风1号方治疗脑出血作用靶点,并分析其生物学功能。方法首先在TCMSP、TCMID及化学专业数据库中收集自拟出血性中风1号方化学成分及作用靶点,利用OMIM、DisGeNET、GeneCards数据库获取与脑出血相关的靶点。利用R软件将自拟出血性中风1号方作用靶点与脑出血相关靶点取交集获取共同靶点(潜在作用靶点);将所得到的共同靶点通过String平台进行蛋白质互相作用(PPI)筛选出自拟出血性中风1号方治疗脑出血的关键靶点。利用metascape数据库及R软件对自拟出血性中风1号方治疗脑出血的关键靶点进行生物学功能分析(GO及KEGG富集分析)。最后利用Pymol、AutoDock Vina将自拟出血性中风1号方核心化学成分与关键靶点进行分子对接验证。结果共收集到自拟出血性中风1号方53种有效中药化学成分,124个药物作用靶点,1896个脑出血相关靶点,最终得到自拟出血性中风1号方治疗脑出血的潜在作用靶点71个。PPI筛选出的关键靶点包括JUN、TP53、AKT1、VEGFA等。GO共富集到1715个条目,主要涉及到氧化应激、细胞凋亡等方面;KEGG通路富集到130个条目,主要包括PI3K-AKT信号通路、P53信号通路、cAMP信号通路、NF-κB信号通路等。分子对接结果显示中风1号方核心化学成分与关键靶点结合能力较强。结论中风1号方治疗脑出血的作用靶点包括JUN、TP53、AKT1、VEGFA等,生物学功能主要是抑制炎症反应及细胞凋亡、降低氧化应激,相关信号通路主要有PI3K-AKT、P53、cAMP、NF-κB等信号通路。

Objective To analyze the potential targets of self-designed Zhongfeng 1 prescription in treatment of cere⁃bral hemorrhage,and to analyze their biological functions.Methods Firstly,the chemical components and targets of the self-designed Zhongfeng 1 prescription were collected from TCMSP,TCMID and Chemistry Database.The targets of intracerebral hemorrhage were obtained from OMIM,DisgenET and GeneCards database.Using R software,the self-designed Zhongfeng 1 was interacted with cerebral hemorrhage-related targets to obtain the common targets(potential therapeutic target).The obtained common targets were screened by protein-protein interaction(PPI)on the STRING platform to identify the key targets for the treatment of cerebral hemorrhage.Metascape database and R software were used to ana⁃lyze the biological functions(GO and KEGG enrichment analysis)of the key targets of the prescription in the treatment of cerebral hemorrhage.Finally,PyMoL and Autodock Vina were used to verify the core chemical components of the prescription with the key targets for molecular docking.Results A total of 53 effective TCM chemical components,and 124 targets for drug action and 1896 intracerebral hemorrhage-related targets were collected,and 71 potential therapeutic targets of the self-designed Zhongfeng 1 prescription were finally obtained.The key targets screened by PPI included JUN,TP53,AKT1,VEGFA,etc.A total of 1715 GO items were enriched,and they were mainly involved in the oxidative stress,apoptotic signaling pathway,etc.Totally 130 items were enriched from KEGG pathway,mainly including PI3K-Akt signaling pathway,P53 signaling pathway,cAMP signaling pathway,NF-κB signaling pathway,etc.The molecular docking results showed that the core chemical components had strong binding ability to the target.Conclusion The core targets of self-designed Zhongfeng 1 prescription in the treatment of cerebral hemorrhage include Jun,TP53,Akt1,and VEGFA,etc,they inhibit the inflammatory response and apoptosis,reduce oxidative stress;the related signal pathways mainly include PI3K-AKT,P53,cAMP,NF-κB,and other signal pathways.