药学学报, 2019, 54(9): 1588-1596
引用本文:
沈霞, 任丹, 高静, 张岗, 王永华, 彭亮, 裴丽珊. 基于网络药理学复方龙脉宁方治疗脑卒中的分子机制研究[J]. 药学学报, 2019, 54(9): 1588-1596.
SHEN Xia, REN Dan, GAO Jing, ZHANG Gang, WANG Yong-hua, PENG Liang, PEI Li-shan. The molecular mechanism of stroke treatment by Fufang Longmai Ningfang based on network pharmacology[J]. Acta Pharmaceutica Sinica, 2019, 54(9): 1588-1596.

基于网络药理学复方龙脉宁方治疗脑卒中的分子机制研究
沈霞1, 任丹1, 高静1, 张岗1, 王永华2, 彭亮1, 裴丽珊1
1. 陕西中医药大学药学院, 陕西 咸阳 712046;
2. 西北大学, 陕西 西安 710069
摘要:
脑卒中作为一种常见的疾病,其临床表现复杂多样。复方龙脉宁方治疗脑卒中有着特别明显的疗效,但其治疗脑卒中的分子机制尚不明确。本研究旨在运用网络药理学方法,研究复方龙脉宁方治疗脑卒中的活性成分、作用靶点和分子通路,揭示复方龙脉宁方治疗缺血性脑卒中的分子机制。通过查询TCMSP数据库获取复方龙脉宁方治疗脑卒中的潜在活性成分,利用CNKI数据库来进行文献的验证,通过PharmMapper、UniProt数据库来进行靶点的预测和筛选,利用收集结果通过TTD数据库来进行靶蛋白群的收集,运用Cytoscape软件分别构建"成分-靶点"网络图、"成分-靶点-疾病"网络图、"靶蛋白相互作用"网络图。利用EAGLE算法进行聚类分析,KEGG数据库进行通路分析、SYBYL软件进行分子对接。最终收集得到与脑卒中相关的39个潜在活性成分与17个潜在有效靶点,其代表性活性成分分别是川芎嗪、薯蓣皂苷、葛根异黄酮类等,与之相关的靶点分别是MMP9、NOS3、NOS2、KDR、ALB、IL2、TGFB2、CPB等。研究发现碳代谢和HIF-1信号通路为复方龙脉宁方治疗脑卒中的主要分子通路。阐明复方龙脉宁方治疗缺血性脑卒中可能是通过减少炎症反应、增强血管通透性、抑制脑缺血-再灌注损伤的作用途径,为临床用药提供理论依据。
关键词:    网络药理学      复方龙脉宁方      脑卒中      缺血性脑卒中      靶点     
The molecular mechanism of stroke treatment by Fufang Longmai Ningfang based on network pharmacology
SHEN Xia1, REN Dan1, GAO Jing1, ZHANG Gang1, WANG Yong-hua2, PENG Liang1, PEI Li-shan1
1. School of Pharmacy, Shaanxi University of Chinese Medicine, Xianyang 712046, China;
2. Northwest University, Xi'an 710069, China
Abstract:
Stroke is a common disease with complex and diverse clinical manifestations. Fufang Longmai Ningfang has been found to exhibit therapeutic effect on stroke, but its molecular mechanism for treating stroke remains unclear. The aim of this study was to investigate the molecular mechanism of Fufang Longmai Ningfang in the treatment of ischemic stroke by using the method of network pharmacology to define the active ingredients, target and molecular pathway of Fufang Longmai Ningfang. The TCMSP database was used to obtain the potential active components of Fufang Longmai Ningfang in the treatment of stroke. The CNKI database was used to verify the literature. The target was predicted and screened by PharmMapper and UniProt database. The target protein group was collected by TTD database. The Cytoscape software was used to construct a "component-target" network map, "component-target-disease" network map, and "target protein interaction" network map. The EAGLE algorithm was used for cluster analysis, the KEGG database was used for pathway analysis, and the SYBYL software was used for molecular docking for bioactivity verification. We found 39 potential active ingredients and 17 potential effective targets related to stroke. The representative active ingredients were ligustrazine, dioscin, and puerarin, and the related targets were MMP9, NOS3, NOS2, KDR, ALB, IL2, TGFB2, and CPB among others. The study found that carbon metabolism and HIF-1 signaling pathway are the main molecular pathways for treatment of stroke by Fufang Longmai Ningfang. The treatment of ischemic stroke by Fufang Longmai Ningfang may involve reduction of inflammatory response, enhancement of vascular permeability and inhibition of cerebral ischemia-reperfusion injury, providing a theoretical basis for their clinical use.
Key words:    network pharmacology    Fufang Longmai Ningfang    stroke    ischemic stroke    target   
收稿日期: 2019-01-09
DOI: 10.16438/j.0513-4870.2019-0031
基金项目: 国家自然科学基金资助项目(31600320);陕西省自然科学基金资助项目(2017JM8030);陕西省普通高校青年杰出人才项目.
通讯作者: 高静,Tel:86-29-38185165,E-mail:jxrain@163.com;王永华,E-mail:dcpwyh@163.com
Email: jxrain@163.com;dcpwyh@163.com
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