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基于整合药理学方法探究当归补血汤调控动脉粥样硬化疾病网络的作用机制。

Exploring the mechanism of Danggui Buxue Decoction in regulating atherosclerotic disease network based on integrated pharmacological methods.

机构信息

School of Integrated traditional Chinese and Western Medicine, Hunan University of Chinese Medicine, Changsha, Hunan Province, China.

Department of Cardiology, The First Affiliated Hospital of University of South China, Hengyang, Hunan Province, China.

出版信息

Biosci Rep. 2021 Oct 29;41(10). doi: 10.1042/BSR20211429.

Abstract

OBJECTIVE

To explore the mechanism of Danggui Buxue Decoction (DGBXD) in regulating Atherosclerosis (AS) network based on integrated pharmacological methods.

METHODS

The active ingredients and targets of DGBXD are obtained from TCMSP database and ETCM. AS-related targets were collected from the Genecards and OMIM databases. The drug-disease protein interaction (PPI) networks were constructed by Cytoscape. Meanwhile, it was used to screen out densely interacting regions, namely clusters. Finally, Gene Ontology (GO) annotations are performed on the targets and genes in the cluster to obtain biological processes, and Kyoto Encyclopedia of Genes and Genomes (KEGG) annotations are performed on the targets of the PPI network to obtain signaling pathways.

RESULTS

A total of 212 known targets, 265 potential targets and 229 AS genes were obtained. The 'DGBXD known-AS PPI network' and 'DGBXD-AS PPI Network' were constructed and analyzed. DGBXD can regulate inflammation, platelet activation, endothelial cell apoptosis, oxidative stress, lipid metabolism, vascular smooth muscle proliferation, angiogenesis, TNF, HIF-1, FoxO signaling pathway, etc. The experimental data showed that compared with the model group, the expressions of ICAM-1, VCAM-1, and interleukin (IL)-1β protein and mRNA in the DGBXD group decreased (P<0.05). However, plasma IL-1β, TNF-α, and MCP-1 in the DGBXD group were not significantly different from the model group (P>0.05).

CONCLUSION

The mechanism of DGBXD in the treatment of AS may be related to the improvement of extracellular matrix (ECM) deposition in the blood vessel wall and the anti-vascular local inflammatory response, which may provide a reference for the study of the mechanism of DGBXD.

摘要

目的

基于整合药理学方法探讨当归补血汤调控动脉粥样硬化(AS)网络的作用机制。

方法

从 TCMSP 数据库和 ETCM 数据库中获取当归补血汤的活性成分和靶点;从 Genecards 和 OMIM 数据库中收集 AS 相关靶点;使用 Cytoscape 构建药物-疾病蛋白相互作用(PPI)网络,同时筛选出相互作用密集的区域,即聚类;最后对聚类中的靶点和基因进行基因本体(GO)注释,得到生物过程,对 PPI 网络的靶点进行京都基因与基因组百科全书(KEGG)注释,得到信号通路。

结果

共获得 212 个已知靶点、265 个潜在靶点和 229 个 AS 基因。构建并分析了“当归补血汤已知-AS PPI 网络”和“当归补血汤-AS PPI 网络”。当归补血汤可以调控炎症、血小板激活、血管内皮细胞凋亡、氧化应激、脂质代谢、血管平滑肌增殖、血管生成、TNF、HIF-1、FoxO 信号通路等。实验数据显示,与模型组相比,当归补血汤组 ICAM-1、VCAM-1 和白细胞介素(IL)-1β 蛋白及 mRNA 表达降低(P<0.05),但当归补血汤组血浆中 IL-1β、TNF-α 和 MCP-1 与模型组相比差异无统计学意义(P>0.05)。

结论

当归补血汤治疗 AS 的作用机制可能与改善血管壁细胞外基质(ECM)沉积和抗血管局部炎症反应有关,为研究当归补血汤作用机制提供参考。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/59e9/8521537/f0c6da756321/bsr-41-bsr20211429-g1.jpg

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