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基于 cheminformatics 和转录组学策略探讨脑泰方对血管性痴呆的生物网络的调控机制。

Exploring the regulatory mechanism of Nao Tai Fang on vascular Dementia's biological network based on cheminformatics and transcriptomics strategy.

机构信息

Hunan University of Chinese Medicine, Hunan, China.

Hunan University of Chinese Medicine, Hunan, China; Capital Medical University, Beijing, China.

出版信息

J Ethnopharmacol. 2021 Jun 28;274:114065. doi: 10.1016/j.jep.2021.114065. Epub 2021 Mar 23.

Abstract

ETHNOPHARMACOLOGICAL RELEVANCE

Nao Tai Fang (NTF) is modified from Buyang Huanwu Decoction. Modern pharmacological research showed that NTF has a good anti-cerebral ischemic effect and can improve the learning and memory ability of cerebrovascular disease.

AIM

The purpose of this study is to explore the regulation mechanism of NTF on the regulation mechanism of vascular dementia (VD)'s biological network based on chemoinformatics and transcriptomics strategies.

METHOD

First, the bilateral common carotid artery ligation method was used to create a rat VD model. After NTF intervention for 30 days, the treatment effect was evaluated by HE staining and water maze experiment. Then, the Agilent mRNA expression profiling chip was used to obtain mRNA expression data of hippocampal tissues of VD model rats before and after NTF intervention, and microarray analysis was used to screen for genes with significant differential expression. The BATMAN database was utilized to obtain the potential targets of NTF and the Genecards and OMIM were utilized to collect the VD potential genes. The cytoscape was utilized to construct and analyze the networks.

RESULT

The animal experiments showed that NTF can improve VD. A total of 180 up-regulated proteins and 289 down-regulated proteins were identified. The top 20 up- and down-regulated differentially expressed genes were utilized to construct differentially expressed gene's protein-protein interaction (PPI) network. A total of 677 NTF potential targets and 550 VD genes were obtained and were utilized to construct NTF-VD PPI network. The cheminformatics analysis showed that NTF can regulate a lot of biological processes and signaling pathways (such as inflammation modules, vasodilation and contraction modules, hypoxia modules, angiogenesis, coagulation, neurovascular unit modules, Neuroactive ligand-receptor interaction, Calcium signaling pathway, Serotonergic synapse).

CONCLUSION

NTF may play a role in the treatment of VD through the targets, signaling pathways and biological processes discovered in this study.

摘要

民族药理学相关性

脑泰方(NTF)是由补阳还五汤改良而来。现代药理学研究表明,NTF 具有良好的抗脑缺血作用,能改善脑血管病患者的学习记忆能力。

目的

本研究旨在基于化学信息学和转录组学策略,探讨 NTF 对血管性痴呆(VD)生物网络调控机制的调节作用。

方法

首先采用双侧颈总动脉结扎法建立大鼠 VD 模型,NTF 干预 30 天后,通过 HE 染色和水迷宫实验评价其治疗效果。然后采用 Agilent mRNA 表达谱芯片获取 VD 模型大鼠海马组织经 NTF 干预前后的 mRNA 表达数据,采用微阵列分析筛选出差异表达显著的基因。利用 BATMAN 数据库获取 NTF 的潜在靶点,利用 Genecards 和 OMIM 收集 VD 的潜在基因。运用 cytoscape 构建并分析网络。

结果

动物实验表明,NTF 可改善 VD。共鉴定出 180 个上调蛋白和 289 个下调蛋白。利用前 20 个上调和下调差异表达基因构建差异表达基因蛋白-蛋白相互作用(PPI)网络,共获得 677 个 NTF 潜在靶点和 550 个 VD 基因,构建 NTF-VD PPI 网络。化学信息学分析表明,NTF 可调控多种生物过程和信号通路(如炎症模块、血管舒张和收缩模块、缺氧模块、血管生成、凝血、神经血管单元模块、神经活性配体-受体相互作用、钙信号通路、血清素能突触)。

结论

本研究发现的 NTF 作用靶点、信号通路和生物过程可能参与了 NTF 治疗 VD 的作用。

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