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多维度网络比较分析揭示了黄芩苷在小鼠脑缺血靶向网络中的纯药理机制。

Poly-dimensional network comparative analysis reveals the pure pharmacological mechanism of baicalin in the targeted network of mouse cerebral ischemia.

作者信息

Liu Qiong, Liu Jun, Wang Pengqian, Zhang Yingying, Li Bing, Yu Yanan, Dang Haixia, Li Haixia, Zhang Xiaoxu, Wang Zhong

机构信息

Institute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences, No. 16 Nanxiaojie, Dongzhimennei, Beijing 100700, China.

Dongzhimen Hospital, Beijing University of Chinese Medicine, No. 16 Nanxiaojie, Dongzhimennei, Beijing 100700, China.

出版信息

Brain Res. 2017 Jul 1;1666:70-79. doi: 10.1016/j.brainres.2017.04.008. Epub 2017 Apr 29.

DOI:10.1016/j.brainres.2017.04.008
PMID:28465229
Abstract

AIM

This study aimed to investigate the pure pharmacological mechanisms of baicalin/baicalein (BA) in the targeted network of mouse cerebral ischemia using a poly-dimensional network comparative analysis.

METHODS

Eighty mice with induced focal cerebral ischemia were randomly divided into four groups: BA, Concha Margaritifera (CM), vehicle and sham group. A poly-dimensional comparative analysis of the expression levels of 374 stroke-related genes in each of the four groups was performed using MetaCore.

RESULTS

BA significantly reduced the ischemic infarct volume (P<0.05), whereas CM was ineffective. Two processes and 10 network nodes were shared between "BA vs CM" and vehicle, but there were no overlapping pathways. Two pathways, three processes and 12 network nodes overlapped in "BA vs CM" and BA. The pure pharmacological mechanism of BA resulted in targeting of pathways related to development, G-protein signaling, apoptosis, signal transduction and immunity. The biological processes affected by BA were primarily found to correlate with apoptotic, anti-apoptotic and neurophysiological processes. Three network nodes changed from up-regulation to down-regulation, while mitogen-activated protein kinase kinase 6 (MAP2K6, also known as MEK6) changed from down-regulation to up-regulation in "BA vs CM" and vehicle. The changed nodes were all related to cell death and development.

CONCLUSION

The pure pharmacological mechanism of BA is related to immunity, apoptosis, development, cytoskeletal remodeling, transduction and neurophysiology, as ascertained using a poly-dimensional network comparative analysis.

摘要

目的

本研究旨在通过多维度网络比较分析,探讨黄芩苷/黄芩素(BA)在小鼠脑缺血靶向网络中的纯药理机制。

方法

将80只诱导局灶性脑缺血的小鼠随机分为四组:BA组、珍珠母(CM)组、溶媒组和假手术组。使用MetaCore对四组中374个与中风相关基因的表达水平进行多维度比较分析。

结果

BA显著降低了缺血梗死体积(P<0.05),而CM无效。“BA与CM”组和溶媒组之间共有两个过程和10个网络节点,但没有重叠的通路。“BA与CM”组和BA组中有两条通路、三个过程和12个网络节点重叠。BA的纯药理机制导致其靶向与发育、G蛋白信号传导、凋亡、信号转导和免疫相关的通路。发现受BA影响的生物学过程主要与凋亡、抗凋亡和神经生理过程相关。在“BA与CM”组和溶媒组中,三个网络节点从上调变为下调,而丝裂原活化蛋白激酶激酶6(MAP2K6,也称为MEK6)从下调变为上调。这些变化的节点均与细胞死亡和发育有关。

结论

通过多维度网络比较分析确定,BA的纯药理机制与免疫、凋亡、发育、细胞骨架重塑、转导和神经生理有关。

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