生信分析肾阴虚型绝经后骨质疏松症分子机制及熟地黄靶向治疗
Bioinformatics analysis of molecular mechanism of postmenopausal osteoporosis with kidney-yin deficiency and targeting of Rehmanniae
  
DOI:10.3969/j.issn.1006-7108.2021.04.014
中文关键词:  骨质疏松症  熟地黄  肾阴虚  绝经后  通路  病理机制
英文关键词:osteoporosis  Rehmanniae  kidney-yin deficiency  postmenopausal  pathway  pathological mechanism
基金项目:广东省中医药局面上科研项目(20191292,20201298);深圳市科技创新委员会研究项目(JCYJ20180302144355408,JCYJ20190808100818959)
作者单位
韩林静1 吴克亮1 王宏波2 肖庆华2 张震2 朱建宗2 林晓生2* 1.广州中医药大学广东 广州 510405 2.深圳市中西医结合医院广东 深圳 518104 
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中文摘要:
      目的 基于生信数据挖掘探究肾阴虚型绝经后骨质疏松症的病理机制及熟地黄的治疗靶点。方法 通过GEO数据库挖掘阴虚型绝经后骨质疏松症患者差异表达基因,运用GeneCards及OMIM数据库预测骨质疏松症相关基因,采用R软件对阴虚靶点与骨质疏松靶点映射匹配。借助String数据库在线平台进行蛋白互作网络构建。分子对接预测熟地黄治疗阴虚型骨质疏松症的靶点。采用DAVID数据库进行生物过程及通路注释。结果 通过分析得到差异表达基因1 272个,骨质疏松症靶点662个,阴虚型骨质疏松症相关靶点45个,主要涉及细胞凋亡调节、雌激素应答、骨骼肌系统发育等生物过程,并由PI3K-Akt、Wnt信号通路、MAPK信号通路、卵巢类固醇生成等信号通路调节。熟地2种有效成分能够作用于核心蛋白IGF1、VEGFA等。结论 熟地黄可能靶向IGF1、VEGFA等核心蛋白,通过PI3K-Akt、MAPK等信号通路调节细胞凋亡及雌激素应答过程,从而实现防治阴虚型骨质疏松症的疗效。
英文摘要:
      Objective To explore the pathological mechanism of postmenopausal osteoporosis of kidney-yin deficiency and the therapeutic target of Rehmanniae by bio-information data analysis. Methods The differentially expressed genes in postmenopausal osteoporosis patients with yin deficiency were analysed in GEO database. GeneCards and OMIM database were used to predict osteoporosis-related genes, and R software was used to map a Venn diagram of yin deficiency and osteoporosis matching. Use the String database online platform for protein interaction network construction. Molecular docking predicts the targets of Rehmanniae in the treatment of osteoporosis of yin deficiency. Use the DAVID database to annotate biological processes and pathways. Results Through analysis, 1272 differentially expressed genes, 662 osteoporosis related targets, and 45 yin deficiency osteoporosis related targets were obtained, mainly involving biological processes such as apoptosis regulation, estrogen response, and skeletal system development. It was regulated by PI3K-Akt, Wnt signaling pathway, MAPK signaling pathway, Ovarian steroidogenesis and some other signaling pathways. The two active ingredients of Rehmanniae could act on the hub proteins IGF1, VEGFA, etc. Conclusion Rehmanniae can target hub proteins such as IGF1 and VEGFA, regulate the apoptosis and estrogen response via PI3K-Akt, MAPK signaling pathway and some other signaling pathways, so as to achieve the effect of preventing and treating yin deficiency osteoporosis.
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