生当归和酒当归不同组分活血作用的差异性及其机制研究  

Studies on Differences and Mechanisms of Various Fractions Extracted from Angelicae Sinensis Radix and Wine-Processed Angelicae Sinensis Radix on Activating Blood Circulation

作　　者：毛雨洁 张少萌 郭双岩 史永洁 董高攀 闫慧娟 张来宾[1] 吕洁丽[1] MAO Yu-jie;ZHANG Shao-meng;GUO Shuang-yan;SHI Yong-jie;DONG Gao-pan;YAN Hui-juan;ZHANG Lai-bin;LYU Jie-li(School of Pharmacy,Xinxiang Medical University,Xinxiang 453003,China)

机构地区：[1]新乡医学院药学院,河南新乡453003

出　　处：《南京中医药大学学报》2023年第10期1015-1033,共19页Journal of Nanjing University of Traditional Chinese Medicine

基　　金：国家自然科学基金面上项目(81773898);河南省优秀青年科学基金项目(212300410066)。

摘　　要：目的基于网络药理学和动物实验开展生当归和酒当归不同组分活血作用的差异性研究,并探讨其潜在机制。方法借助网络药理学方法,从药物成分及疾病相关数据库预测当归的成分作用靶点及血瘀证(Blood stasis,BS)相关靶点,根据拓扑特征值筛选关键靶点、核心成分后,进行基因本体(Gene ontology,GO)功能及京都基因与基因组百科全书(Kyoto encyclopedia of genes and genomes,KEGG)通路富集分析;采用皮下注射肾上腺素加冰水浴法诱导的急性血瘀大鼠模型开展生当归和酒当归不同组分活血作用的差异性研究,并对预测的关键靶点及通路进行机制验证。结果网络药理学结果表明,当归134个潜在活性成分含有1062个相关靶点,血瘀证相关靶点476个,交集靶点145个。根据拓扑特征值筛选出当归治疗血瘀证的关键靶点15个,与关键靶点关联的核心成分36个;富集分析发现关键靶点主要与血管内皮生长因子产生(Vascular endotheial growth factor production)、一氧化氮生物合成过程的正调控(Positive regulation of nitric oxide biosynthetic process)、对缺氧的反应(Cellular response to hypoxia)等生物过程,以及血管内皮生长因子(Vascular endothelial growth factor,VEGF)信号通路、磷脂酰肌醇-3-激酶/蛋白激酶B(Phosphatidylinositol 3-kinase/protein kinase B,PI3K/AKT)信号通路、肿瘤坏死因子(Tumor necrosis factor,TNF)信号通路等有关。动物实验结果显示:与模型组相比,酒当归正丁醇组分(WASB)具有较强的活血作用,可显著改善血瘀模型大鼠的外观形态学和组织病理学表现,降低脏器指数,抑制炎性介质[一氧化氮(Nitric oxide,NO)、前列腺素E2(Prostaglandin E2,PGE2)、肿瘤坏死因子-α(Tumor necrosis factor-α,TNF-α)]的释放、抑制氧化应激,显著下调VEGFA的蛋白表达,抑制AKT、PI3K蛋白的磷酸化(P<0.05,P<0.01,P<0.001),其他组分对急性血瘀模型大鼠活血作用不及该组分,且生、酒当�OBJECTIVE To explore the differences and the mechanisms of various fractions extracted from Angelicae Sinensis Radix(AS)and wine-processed Angelicae Sinensis Radix(WAS)on activating blood circulation based on network pharmacology and animal experiments validation.METHODS Drug targets of AS and blood stasis(BS)-associated targets were screened from disease and drug related database,and the key targets and the core components were screened according to topological eigenvalues.Gene ontology(GO)function and Kyoto encyclopedia of genes and genomes(KEGG)enrichment analysis were performed.The acute blood stasis model in rats induced by adrenaline hydrochloride and ice-water bath was used to explore the differences of various fractions extracted from AS and WAS.And then the screened targets based on network pharmacology were further verified.RESULTS A total of 134 potential active components,1062 targets of AS,476 BS-associated targets,145 common targets,15 key targets and 36 core components were obtained.Enrichment analysis showed that the key targets were mainly involved in biological processes such as vascular endothelial growth factor production,positive regulation of nitric oxide biosynthetic process and cellular response to hypoxia,as well as Vascular endothelial growth factor(VEGF)signaling pathway,Phosphatidylinositol 3-kinase/protein kinase B(PI3K/AKT)signaling pathway,and Tumor necrosis factor(TNF)signaling pathway.The results of animal experiments showed that compared with the model group,the effect of activating circulation of n-butyl alcohol-soluble fraction from WAS(WASB)was superior to those of other fractions.WASB remarkably improved the histopathological manifestations and appearance morphological characteristics of the acute blood stasis model in rats,significantly reduced organ index,evidently inhibited the release of inflammatory mediators(Nitric oxide,NO;Prostaglandin E 2,PGE 2;Tumor necrosis factor-α,TNF-α),suppressed oxidative stress,and significantly restrained the expression of VEGFA and the ph

关 键 词：当归 酒炙 血瘀证 网络药理学 氧化应激 VEGFA PI3K/AKT 

分 类 号：R285.5[医药卫生—中药学]