基于网络药理学和分子对接方法研究清养活血汤治疗卒中相关性肺炎的作用机制

Study on the mechanism of Qingyang Huoxue Tang in treating stroke associated pneumonia based on network pharmacology and molecular docking methods

目的 基于网络药理学和分子对接技术探究清养活血汤治疗卒中相关性肺炎(SAP)的分子作用机制。方法 采用中药系统药理学数据库与分析平台(TCMSP)筛选清养活血汤的活性成分及潜在作用靶点,利用GeneCards、OMIM、PharmGkb、TTD和DrugBank数据库检索SAP疾病的靶点,并通过R软件“venn”包对药物潜在作用靶点与疾病相关作用靶点取交集得到共同作用靶点。利用Cytoscape软件及STRING数据库,建立清养活血汤治疗SAP的潜在活性成分-靶点调控网络模型及交集靶点蛋白互作网络,分析网络中关键靶点基因及对应药物活性成分。通过基因本体(GO)功能分析和京都基因与基因组百科全书(KEGG)通路富集分析。利用分子对接技术验证核心成分与靶蛋白分子的对接情况。结果 TCSMP数据库筛选得到清养活血汤共15味中药,有效活性成分160个,作用靶点447个,筛选得到SAP疾病潜在靶点4 425个,作用于该疾病的潜在靶点282个,核心作用靶点21个。GO富集分析显示,在生物学进程,关键靶点基因主要富集于脂多糖的反应,在分子功能和细胞成分上,关键靶点基因主要富集于核受体活性和膜筏等方面;KEGG富集分析表明,关键靶点基因主要富集于脂质和动脉粥样硬化和AGE-RAGE信号通路。通过分子对接显示,清养活血汤主要活性成分与核心靶蛋白结合具有较好的亲和力。结论 清养活血汤具有多活性成分,能够通过抗炎、抗氧化、改善血管功能等多种途径发挥治疗SAP的作用,可为临床清养活血汤治疗SAP进一步研究提供科学依据。

Objective To explore the molecular mechanism of Qingyang Huoxue Tang in the treatment of stroke related pneumonia based on network pharmacology and molecular docking technology.Methods Used the Traditional Chinese Medicine System Pharmacology Database and Analysis Platform(TCMSP)to screen the active ingredients and potential targets of Qingyang Huoxue Tang.Used GeneCards,OMIM,PharmaGkb,TTD,and DrugBank databases to search for targets of stroke related pneumonia disease,and intersected the potential targets of the drug and disease related targets to obtain common targets of action by Venn.Using Cytoscape software and STRING database,established a potential active ingredient target regulatory network model and intersection target protein interaction network for the treatment of stroke associated pneumonia with Qingyang Huoxue Tang,analyzed key target genes and corresponding drug active ingredients in the network.Through gene ontology(GO)functional analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis.Verified the docking between core components and target protein molecules using molecular docking technology.Results The TCSMP database screened a total of 15 traditional Chinese medicines,including 160 active ingredients and 447 targets,and identified 4425 potential targets for stroke related pneumonia disease,282 potential targets for this disease,and 21 core targets.GO enrichment analysis showed that in biological processes,key target genes were mainly enriched in the response of lipopolysaccharides.In terms of molecular function and cellular composition,key target genes were mainly enriched in nuclear receptor activity and membrane rafts;KEGG enrichment analysis showed that key target genes were mainly enriched in lipids,atherosclerosis and AGE-RAGE signaling pathway.Through molecular docking,it was shown that the main active ingredients of Qingyang Huoxue Tang had good affinity for binding to core target proteins.Conclusion Qingyang Huoxue Tang has multiple active ingredients and can exert the therapeutic effect on stroke related pneumonia through various pathways such as anti-inflammatory,antioxidant and improving vascular function.It can provide scientific basis for further clinical research on the treatment of stroke related pneumonia with Qingyang Huoxue Tang.