基于多组学技术探讨补肾化痰方防止绝经后骨质疏松症的作用机制

The mechanism of Bushen Huatan Recipe on preventing postmenopausal osteoporosis based on multi-omics techniques

目的 通过网络药理学与基因组测序观察补肾化痰方对绝经后骨质疏松的作用机理。方法研究利用TCMSP、ETCM、BATMAN-TCM数据库获得补肾化痰方有效活性成分并收集靶点信息,在OMIM、MalaCard、GeneCards数据库提取与PMOP相关的疾病靶点。通过String平台分别构建了补肾化痰方和PMOP基因互作网,并寻找了2个网络的相交靶标。通过基因本体(GO)和KEGG富集分析得到补肾化痰方防治PMOP的分子靶点和通路。建立PMOP大鼠模型,给予补肾化痰方后取外周血清进行全转录组测序获得差异表达基因。并利用Metascape网站将差异表达基因进行GO功能和KEGG通路富集分析。结果 补肾化痰方有54种有效活性成分,作用于PMOP的靶点259个。补肾化痰方调控差异基因的富集通路主要参与免疫炎症、炎症因子调控、破骨细胞分化、转录因子、氧化还原酶,以及转移酶、外源物质的代谢以及免疫细胞受体的信号传导。结论 补肾化痰方通过多种有效的活性成分,多途径作用于PMOP,其机制可能以抗炎与调节骨免疫为核心,通过参与成骨/破骨细胞的分化、增殖、凋亡,达到防治PMOP的作用。

Observe To observe the mechanism of Bushen Huatan Recipe on postmenopausal osteoporosis by network pharmacology and genome sequencing. Methods Obtained the active ingredients of Bushen Huatan Recipe from TCMSP,ETCM and Batman-TCM databases and collected target information,then acquired PMOP related disease targets from OMIM,MalaCard and GeneCards databases. The interaction networks of Bushen Huatan Recipe and PMOP protein network were established respectively via String platform,and selected the intersection targets of the two networks. The molecular targets and pathways of Bushen Huatan Recipe against PMOP were obtained by gene body(GO)and KEGG enrichment analysis. Established PMOP rat model,obtain the dissimilarlyexpressed genes in peripheral blood for total transcriptome sequencing after the treatment with Bushen Huatan Recipe. The differentially expressed genes were analysed for GO function and KEGG pathway enrichment by Metascape website. Results There were 54 active components,acted on 259 targets of PMOP in Bushen Huatan Recipe.The enrichment pathways of differential genes regulated by Bushen Huatan Recipe were mainly involved in immune inflammation,regulation of inflammatory factors,osteoclast differentiation,transcription factors,oxidoreductase,metabolism of transferase and exogenous substances,and signal transduction of immune cell receptors. Conclusion Bushen Huatan Recipe acts on PMOP through a variety of effective active components in multiple ways,its mechanism may be anti-inflammatory and bone immunity regulation,through participating in the differentiation,proliferation and apoptosis of osteogenic/osteoclast cells,PMOP can b prevented and treated.