基于网络药理学方法探讨桃红四物汤防治 股骨头坏死的潜在分子机制

The Mechanism of Taohong Siwu Decoction in the Treatment of Osteonecrosis of the Femoral Head Based on Network Pharmacology

目的运用网络药理学的方法,探索桃红四物汤防治股骨头坏死的可能分子机制,为基础实验研究提供新方向。方法通过TCMSP平台获取桃红四物汤的相关活性成分及作用靶点;从GeneCards以及OMIM数据库获取与股骨头坏死相关的靶点基因,两者的交集即为桃红四物汤-股骨头坏死疾病交集基因。采用STRING平台构建靶标基因蛋白互作网络(PPI);利用Cytoscape3.7.1软件构建桃红四物汤-靶标-疾病调控网络,筛选核心靶点基因;最后对交集靶点进行GO功能富集分析与KEGG通路富集分析,统计桃红四物汤-股骨头坏死共同靶标的可能作用机制及相关信号通路。结果通过筛选得到桃红四物汤的69个有效成分和160个作用靶点,从GeneCards以及OMIM数据库筛选得到股骨头坏死相关靶点基因245个,取其交集得到桃红四物汤-股骨头坏死疾病交集基因39个。筛选后得到核心靶点基因21个,并推断其作用机制可能与糖尿病并发症的晚期糖基化终末产物-晚期糖基化终末产物受体信号通路、白介素-17信号通路、低氧诱导因子-1信号通路、松弛肽信号通路、磷脂酰肌醇3-激酶/蛋白激酶B信号通路等有关,且白介素-6基因、血管内皮生长因子A基因、表皮生长因子受体基因、基质金属蛋白酶基因可能起到关键性作用。结论多通路、多靶点共同作用是桃红四物汤防治股骨头坏死的一大特点。

Objective To explore the possible molecular mechanism of Taohong Siwu decoction in preventing and treating femoral head necrosis by network pharmacology,and to provide a new direction for basic experimental research.Methods The related active ingredients and targets of Taohong Siwu decoction were obtained by TCMSP platform.The target genes related to femoral head necrosis were obtained from GeneCards and OMIM databases,and the intersection of the two was the intersection gene of Taohong Siwu decoction and femoral head necrosis disease.Target gene protein interaction network(PPI)was constructed by STRING platform.Cytoscape 3.7.1 software was used to construct Taohong Siwu decoction-target-disease regulatory network and screen the core target genes.Finally,GO function enrichment analysis and KEGG pathway enrichment analysis of intersection targets were carried out,and the possible mechanism and related signaling pathways of Taohong Siwu decoction-femoral head necrosis common target were counted.Results A total of 69 effective components and 160 action targets of Taohong Siwu decoction were obtained by screening,and 245 target genes related to femoral head necrosis were obtained from GeneCards and OMIM database,and 39 intersection genes of Taohong Siwu decoction and femoral head necrosis disease were obtained by intersection.Twenty-one core target genes were obtained after screening,and it was speculated that the mechanism of action might be related to the receptor signaling pathway of late glycosylation product-late glycosylation end product,interleukin 17 signaling pathway,hypoxia-inducible factor-1 signaling pathway,relaxation peptide signaling pathway,phosphatidylinositol 3-kinase/protein kinase B signaling pathway and diabetic complications,and interleukin-6 gene,vascular endothelial growth factor A gene,epidermal growth factor receptor gene,and matrix metalloproteinases gene might play a key role.Conclusion The combined action of multiple pathways and multiple targets is a major feature of Taohong Siwu decoction in the prevention and treatment of femoral head necrosis.