药学学报, 2018, 53(9): 1406-1413
引用本文:
邹纯才, 鄢海燕, 魏美玲. 基于网络药理学分析瓜蒌薤白配伍抗心力衰竭的作用机制研究[J]. 药学学报, 2018, 53(9): 1406-1413.
ZOU Chun-cai, YAN Hai-yan, WEI Mei-ling. Study of the anti-heart failure mechanisms of compatibility of Gualou with Xiebai in basis of network pharmacology[J]. Acta Pharmaceutica Sinica, 2018, 53(9): 1406-1413.

基于网络药理学分析瓜蒌薤白配伍抗心力衰竭的作用机制研究
邹纯才1, 鄢海燕1, 魏美玲2
1. 皖南医学院药学院, 安徽 芜湖 241002;
2. 安徽省第二人民医院药学部, 安徽 合肥 230041
摘要:
基于网络药理学预测及大鼠心肌缺血-再灌注损伤模型验证的方法,对瓜蒌薤白配伍抗心力衰竭的作用机制进行探讨。运用Traditional Chinese Medicine Database@Taiwan (TCM Database@Taiwan)、TraditionalChinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP)、Drug Repositioning and AdverseDrug Reaction Chemical-Protein Interactome (DRAR-CPI)、Universal Protein Resource (Uniprot)数据库进行化合物筛选及活性成分靶点预测,借助Database for Annotation,Visualization,and Integrated Discovery (DAVID)数据库进行生物途径和信号通路分析,预测瓜蒌薤白配伍的作用机制。考察瓜蒌薤白滴丸预处理对心肌缺血-再灌注损伤大鼠心肌细胞凋亡及相关信号通路磷脂酰肌醇3-激酶/丝氨酸苏氨酸激酶(phosphatidylinositol-3-kinase/proteinkinase B,PI3K/Akt)中Akt、磷酸化丝氨酸/苏氨酸激酶(phosphorylated protein kinase B,p-Akt)和半胱氨酸天冬氨酸蛋白酶-3(cysteine aspartate-specific proteinase,caspase-3)蛋白表达的影响。发现10α-cucurbita-5,24-diene-3β-ol和macrostemonoside等22个化合物通过多靶点、多生物途径及多通路方式协同抗心力衰竭,涉及激素刺激反应、磷酸化过程、细胞凋亡调控等生物学途径和胰岛素、丝裂原活化蛋白激酶(mitogen-activated protein kinase,MAPK)、细胞凋亡等信号通路。瓜蒌薤白滴丸预处理可通过激活PI3K-Akt信号通路,促进Akt蛋白磷酸化,降低caspase-3蛋白表达,发挥抑制细胞凋亡、保护心肌作用,验证了网络药理学结果,综合阐释了瓜蒌薤白配伍抗心力衰竭的作用机制。
关键词:    瓜蒌薤白      配伍      心力衰竭      网络药理学      心肌缺血再灌注损伤     
Study of the anti-heart failure mechanisms of compatibility of Gualou with Xiebai in basis of network pharmacology
ZOU Chun-cai1, YAN Hai-yan1, WEI Mei-ling2
1. Pharmacy School of Wannan Medical College, Wuhu 241002, China;
2. Pharmacy Department of Anhui No.2 Provincial People's Hospital, Hefei 230041, China
Abstract:
This study was designed to explore the anti heart failure mechanisms of the compatibility of Gualou with Xiebai based on network pharmacology in rat model of myocardial ischemia-reperfusion injury. Using the databases of Traditional Chinese Medicine Database@Taiwan (TCM Database@Taiwan), Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP), Drug Repositioning and Adverse Drug Reaction Chemical-Protein Interactome (DRAR-CPI) and Universal Protein Resource (Uniprot) to screen compounds and predict the target of active components, the Database for Annotation, Visualization, and Integrated Discovery (DAVID) database, we predicted the biological pathway and signal pathway in the compatibility of Gualou with Xiebai. The effects of Gualou Xiebai dropping pills on the apoptosis of myocardial cells and the expression of protein kinase B (Akt), p-Akt and cysteine aspartate-specific proteinase (caspase-3) protein were examined in the related signal pathway phosphatidylinositol-3-kinase/protein kinase B (PI3K/Akt) of myocardial ischemia reperfusion injury in rats. Twenty two compounds, such as 10 α-cucurbita-5,24-diene-3β-ol and macrostemonoside were found to protect rats from heart failure through multiple targets, multiple biological pathways and multiple pathways, involving biological pathways such as hormone stimulation reaction, phosphorylation, apoptosis regulation, and signaling pathways such as insulin, mitogen-activated protein kinase (MAPK), cell apoptosis and so on. After the intervention of Gualou Xiebai dropping pills, the PI3K-Akt signaling pathway was activated to promote the phosphorylation of Akt protein, reduce the expression of caspase-3 protein, inhibit apoptosis and protect the myocardium. The data verify the results of the network pharmacology, and explain the mechanisms of anti-heart failure activity of combination of Gualou with Xiebai.
Key words:    Gualou-Xiebai    compatibility    heart failure    network pharmacology    myocardial ischemia reperfusion injury   
收稿日期: 2018-04-27
DOI: 10.16438/j.0513-4870.2018-0394
基金项目: 安徽高校省级自然科学研究重大项目(KJ2015ZD41,KJ2016SD60).
通讯作者: 鄢海燕,Tel:86-533-3932185,E-mail:yhy0801@126.com
Email: yhy0801@126.com
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