基于网络药理学研究六君子汤治疗慢性阻塞性肺疾病的作用机制

Mechanism of Liujunzi Decoction(六君子汤)Treating Chronic Obstructive Pulmonary Disease Based on Network Pharmacology

目的运用网络药理学技术建立"药效成分-疾病靶标-信号通路"之间的关系,研究六君子汤治疗慢性阻塞性肺疾病(chronic obstructive pulmonary disease,COPD)的作用靶点及信号通路,明确作用机制。方法使用中药系统药理学成分分析平台(TCMSP),获得六君子汤的活性成分及作用靶点,并从Gene Cards数据库收集与慢性阻塞性肺疾病相关的靶标基因,将药物作用靶点和疾病相关靶标基因取交集得到该方治疗慢性阻塞性肺疾病的关键作用靶点,采用Cytoscape 3.7.1软件构建"六君子汤活性成分-潜在靶点-慢性阻塞性肺疾病"网络;采用STRING数据库构建靶蛋白相互作用(PPI)网络。借助R软件对关键作用靶点进行GO分析和KEGG富集。结果共筛选出六君子汤活性成分88个,作用靶点216个,从疾病库中共得到疾病靶点1096个,将药物靶点与疾病靶点取交集获得主要靶标112个。STAT3,AKT1,JUN,IL6,MAPK1,MAPK3,PELA,MAPK14等是六君子汤治疗COPD的主要核心靶点。GO功能富集共得到141个条目(P-value<0.05,Q-value<0.05),主要涉及DNA结合转录激活、细胞因子受体结合、磷酸酶结合、抗氧化活动等代谢过程;KEGG富集共得到153条信号通路(P-value<0.05,Q-value<0.05),与COPD关系密切的有AGE-RAGE信号通路、肿瘤坏死因子信号通路、白介素-17(IL-17)信号通路、C型凝集素受体信号通路、缺氧诱导因子-1型信号通路、细胞凋亡等信号通路。结论六君子汤可通过抗炎、抗氧化、改善气道重塑、改善肺部组织、减轻损伤等作用治疗COPD,为进一步研究提供理论依据。

Objective To establish the relationship of" pharmaceutical components-disease targets-signaling pathways" by using network pharmacology technologyandclarify the therapeutic targets and signaling pathways of Liujunzi Decoction(六君子汤) in the treatment of chronic obstructive pulmonary disease(COPD).Methods Using the TCMSP,the research obtained the active ingredients and the targets of Liujunzi Decoction,collected the target genes of COPD from the Gene Cards databaseand took the intersection of the two to obtain the action targets.Cytoscape 3.7.1 software was used to construct the " Liujunzi Decoction active ingredient-potential target-chronic obstructive pulmonary disease" networkand the target protein-protein interaction(PPI) network from the STRING database.Perform GO analysis and KEGG enrichment of key targets were carried out with the help of R software.Results A total of 88 active ingredients in Liujunzi Decoction were screened out,and 216 targets were obtained.A total of 1096 disease targets were obtained from the disease library,and 112 main targets were obtained by taking the intersection of drug targets and disease targets.STAT3,AKT1,JUN,IL6,MAPK1,MAPK3,PELA and MAPK14 are the main core targets of Liujunzi Decoction in the treatment of COPD.A total of 141 items(P<0.05,Q<0.05)were obtained by GO function enrichment,which mainly involved metabolic processes such as DNA binding transcription activation,cytokine receptor binding,phosphatase bindingand antioxidant activity.Through KEGG enrichment,a total of 153 signaling pathways were obtained(P<0.05,Q<0.05).The AGE-RAGE signaling pathway,tumor necrosis factor signaling pathway,interleukin-17 signaling pathway and C-type lectin receptor signaling pathway were closely related to COPD.Conclusion Liujunzi Decoction can treat COPD through anti-inflammatory,anti-oxidation,improving airway remodeling and lung tissueand reducing injuries.It can provide theoretical basis for further research.