生信分析肾阳虚型绝经后骨质疏松症分子机制及淫羊藿的靶向治疗机制

Bioinformatics Analysis of the Molecular Mechanism of Postmenopausal Osteoporosis with Kidney-yang Deficiency and the Targeted Treatment Mechanism of Epimedium Herb

目的基于生物信息学方法探究肾阳虚型绝经后骨质疏松症的分子机制及淫羊藿的治疗靶点。方法通过GEO挖掘阳虚型绝经后骨质疏松症患者与健康人群的差异基因,运用GeneCards及OMIM预测绝经后骨质疏松症靶点,通过匹配筛选出肾阳虚型绝经后骨质疏松症靶点;通过String构建蛋白互作网络,采用DAVID进行富集分析,利用分子对接预测淫羊藿治疗肾阳虚型骨质疏松症的靶点。结果共得到差异基因509个,其中下调基因313个,上调基因196个;绝经后骨质疏松症靶点1187个,筛选得到阳虚型绝经后骨质疏松症靶点48个;GO富集分析这些靶点主要涉及细胞增殖、细胞迁移等生物过程,KEGG信号通路中差异基因主要富集于PI3K-Akt信号通路、Th17细胞分化等信号通路调节;分子对接显示淫羊藿3种有效成分槲皮素、木犀草素、山柰酚能够作用于EGF、CRP、FOS等核心蛋白。结论肾阳虚型绝经后骨质疏松症可能主要由PI3K-Akt信号通路、Th17细胞分化等信号通路调控,淫羊藿可能靶向EGF、CRP等蛋白,通过PI3K-Akt、Th17细胞分化信号通路调节骨代谢,从而实现防治阳虚型绝经后骨质疏松症。

Objective To explore the molecular mechanism of postmenopausal osteoporosis with kidney-yang deficiency and the therapeutic target of epimedium herb based on bioinformatics methods.Methods The differential genes between postmenopausal osteoporosis patients with kidney-yang deficiency and healthy people were excavated by GEO,and the targets of postmenopausal osteoporosis were predicted by GeneCards and OMIM.The protein interaction network was constructed by String,and DAVID was used for enrichment analysis.Molecular docking was used to predict the target of epimedium herb in the treatment of osteoporosis with kidney-yang deficiency.Results A total of 509 differential genes were obtained,including 313 down-regulated genes and 196 up-regulated genes;1187 targets for postmenopausal osteoporosis,and 48 targets for postmenopausal osteoporosis of kidney-yang deficiency were screened.GO enrichment analysis showed that these targets were mainly involved in biological processes such as cell proliferation and cell migration.The differential genes in KEGG signaling pathway were mainly enriched in PI3K-Akt signaling pathway and Th17 cell differentiation.Molecular docking showed that quercetin,luteolin and kaempferol could act on core proteins such as EGF,CRP and FOS.Conclusion Postmenopausal osteoporosis with kidney-yang deficiency may be mainly regulated by PI3K-Akt signaling pathway,Th17 cell differentiation and other signaling pathways.Epimedium herb may target EGF,CRP and other proteins to regulate bone metabolism through PI3K-Akt and Th17 cell differentiation signaling pathways,so as to prevent and treat postmenopausal osteoporosis with kidney-yang deficiency.