基于网络药理学探讨益骨汤防治骨质疏松症的靶标和机制研究

陈智能; 谢丽丽; 陈华; 闫坤; 李桂锦; 姚新苗

doi:10.16766/j.cnki.issn.1674-4152.002116

基于网络药理学探讨益骨汤防治骨质疏松症的靶标和机制研究

doi: 10.16766/j.cnki.issn.1674-4152.002116

陈智能^{1, 2},
谢丽丽³,
陈华^{1, 2},
闫坤⁴,
李桂锦^{1, 2},
姚新苗^{1, 2, ,}

1.
浙江中医药大学附属第三医院骨伤科，浙江杭州 311005
2.
浙江省中医药重大疾病(脊柱病)防治中心，浙江杭州 311005
3.
杭州市萧山区中医骨伤科医院中医妇科，浙江杭州 311261
4.
浙江中医药大学第三临床医学院，浙江杭州 310053

基金项目:

浙江省自然科学基金重点项目 LZ15H270001

浙江省自然科学基金项目 LY17H270005

浙江省“十三五”中医药重点专科建设项目浙卫办中医[2019]1号

详细信息

通讯作者:
姚新苗, E-mail：yxmtcm@aliyun.com

中图分类号: R681 R285
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- PDF下载量: 1
- 被引次数: 0
出版历程
- 收稿日期: 2020-03-10
- 网络出版日期: 2022-02-15

Network Pharmacology-Based Study on the mechanism and targets of Yigu Decoction in the treatment of osteoporosis

CHEN Zhi-neng^{1, 2},
XIE Li-li³,
CHEN Hua^{1, 2},
YAN Kun⁴,
LI Gui-jin^{1, 2},
YAO Xin-miao^{1, 2
, ,}

1.
Department of Orthopedics and Traumatology, the Third Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, Zhejiang 311005, China

摘要

摘要: 目的探讨益骨汤防治骨质疏松的物质基础及其靶标，阐明益骨汤防治骨质疏松症的潜在靶点和作用机制。方法通过TCMSP等数据库筛选益骨汤组分中的活性成分及其作用靶点。通过OMIM、GeneCards等数据库预测益骨汤治疗骨质疏松症的相关靶点，构建“药物-成分-靶点-疾病”网络。利用Cytoscape软件构建益骨汤组分治疗骨质疏松症的成分作用靶点网络，采用STRING数据库构建PPI网络，利用通过生物学信息注释数据库分析靶点的GO富集和KEGG信号通路。结果共纳入益骨汤6味中药相关的有效活性成分159个，589个药物靶标，按照君臣佐使配对，其中334个靶点有相互作用关系；蛋白互作分析提示INS、AKT1、IL6、MAPK3、VEGFA等为蛋白互作网络中的核心靶点；靶标富集结果显示3 148个GO术语被显著富集(均P < 0.05);PI3K-Akt信号通路、MAPK信号通路、cGMP-PKG信号通路、Wnt信号通路、破骨细胞分化等175个信号通路被显著富集(均P < 0.05)。结论中药复方君臣佐使配伍可以转换为靶标相互作用的化合物形式，阐明益骨汤的物质基础及配伍机制。益骨汤组分靶标和通路不仅具有调节成骨细胞和破骨细胞功能的双重作用，还通过影响和干预骨微循环境，体现补肾健脾活血法治疗骨质疏松的物质基础，符合骨质疏松的病理生理机制。
- 骨质疏松症 /
- 益骨汤 /
- 网络药理学 /
- 分子机制
Abstract: Objective To investigate the molecular basis of Yigu Decoction (YGD) and its predictive targets and clarify the potential targets and mechanisms of YGD in the treatment of osteoporosis. Methods The active components and their targets corresponding to the herbs by traditional Chinese medicine systems pharmacology database (TCMSP) were determined via network pharmacology. The relevant targets of YGD in the treatment of osteoporosis were predicted using OMIM and GeneCards databases. A network of 'drug component-target disease' was constructed. A component-based target network for the treatment of osteoporosis with YGD components was constructed using Cytoscape software. A protein-protein interaction (PPI) network was constructed using STRING database. Gene Ontology (GO) enrichment and KEGG signalling pathways of the targets were analysed using a biological information annotation database. Results A total of 159 effective active components and 589 drug targets related to six herbs were found in YGD. Protein interaction analysis suggested that INS, AKT1, IL6, MAPK3 and VEGFA were the core targets of protein interaction network. A total of 334 targets were retrieved according to their orders, which were further enriched in 3 148 GO terms (all P < 0.05). A total of 175 signalling pathways were significantly enriched (all P < 0.05), including the PI3K-Akt signalling pathway, the MAPK signalling pathway, the cGMP-PKG signalling pathway, the Wnt signalling pathway and osteoclast differentiation. Conclusion The herbs, compounds and targets related to the compounds of YGD are effective carriers for YGD according to their orders. The targets and pathways of YGD not only regulate the functions of osteoblasts and osteoclasts but also intervene in bone microcirculation, which reflect the material basis of the treatment of osteoporosis by Bushen Jianpi Huoxue and conforms to the pathophysiological mechanism of osteoporosis.
- Osteoporosis /
- Yigu Decoction /
- Network pharmacology /
- Molecular mechanism

HTML全文

图 1 组分药物君臣佐使靶点基因分布情况统计图

下载: 全尺寸图片幻灯片

图 2 中药复方治疗骨质疏松症的GO富集分析生物过程

下载: 全尺寸图片幻灯片

图 3 中药复方治疗骨质疏松症的GO富集分析细胞组分

下载: 全尺寸图片幻灯片

图 4 中药复方治疗骨质疏松症的GO富集分析分子功能

下载: 全尺寸图片幻灯片

图 5 中药复方治疗骨质疏松症的KEGG富集分析

下载: 全尺寸图片幻灯片

表 1 药物组中药-成分-靶标基本信息统计表

药物名称	成分数量(个)	预测靶标数量(个)
丹参	68	138
骨碎补	20	174
山药	16	59
仙灵脾	25	225
生地黄	9	104
补骨脂	29	336

下载: 导出CSV

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