基于CMC/UPLC-Q-TOF/MS 探讨稳心颗粒效应成分及 抗心律失常作用机制  

Effective Components and Antiarrhythmic Mechanisms of Wenxin Granules Based on CMC/UPLC-Q-TOF/MS

作　　者：于露 钱舒乐 郭海珍 赵玉珂 李晓凤[2] 杜武勋[2] YU Lu;QIAN Shule;GUO Haizhen;ZHAO Yuke;LI Xiaofeng;DU Wuxun(Tianjin University of Traditional Chinese Medicine(TCM),Tianjin 300383,China;The Second Affiliated Hospital of Tianjin University of TCM,Tianjin 300150,China)

机构地区：[1]天津中医药大学,天津300383 [2]天津中医药大学第二附属医院,天津300150

出　　处：《中国实验方剂学杂志》2024年第19期124-132,共9页Chinese Journal of Experimental Traditional Medical Formulae

基　　金：天津市中医药管理局天津市名中医传承工作建设项目“杜武勋天津市名中医传承工作室”;国家中医药管理局全国名老中医药专家传承工作室建设项目“杜武勋全国名老中医药专家传承工作室”;天津市教委科研计划项目(2019SK025);国家自然科学基金项目(82004329)。

摘　　要：目的:基于细胞膜色谱法(CMC)联合高效液相色谱-四极杆飞行时间串联质谱法(UPLC-Q-TOF/MS)结合网络药理学探讨稳心颗粒(WXKL)效应成分及抗心律失常作用机制。方法:采用CMC/UPLC-Q-TOF/MS鉴定WXKL能够与心肌细胞膜特异性结合的成分,利用SwissTarget Prediction、GeneCards等数据库挖掘WXKL潜在有效成分作用靶点与心律失常相关靶点,Cytoscape软件构建“成分-靶点-疾病”网络,进行GO功能和KEGG通路富集分析,并进行关键成分和靶点的分子对接,最后通过体内实验进一步验证。结果:鉴定到WXKL潜在有效成分共39个,其中13种来源于三七,15种来源于党参,7种来源于甘松,1种来源于黄精,1种来源于琥珀,1种为黄精、党参共有成分,1种为三七、党参共有成分。网络药理学预测WXKL抗心律失常核心靶点16个,79条相关通路,主要涉及心肌细胞中的肾上腺素能信号、环磷酸鸟苷(cGMP)/蛋白激酶G(PKG)、钙离子信号、环腺苷酸(cAMP)、白细胞介素(IL)-17、丝裂原活化蛋白激酶(MAPK)和肿瘤坏死因子(TNF)等通路。大鼠体内实验结果显示,WXKL明显改善了大鼠β_(1)-肾上腺素受体(β_(1)-AR)、cAMP、TNF-α、钙电压门控通道亚基alpha1 C(CACNA1C)的表达。结论:WXKL能够通过多成分、多靶点、多通路发挥抗心律失常的作用,为阐释抗心律失常中药的潜在药效物质基础与作用机制提供科学依据。Objective:To employ the effective components and antiarrhythmic mechanism of Wenxin Granules(WXKL)by cell membrane chromatography(CMC)and ultra-performance liquid chromatographyquadrupole time-of-flight mass spectrometry(UPLC-Q-TOF/MS),combined with network pharmacology.Method:In this study,the CMC/UPLC-Q-TOF/MS technique was employed to identify the components in WXKL that could specifically bind to myocardial cell membranes.By utilizing databases such as SwissTarget Prediction and GeneCards,the targets of WXKL's effective components and arrhythmia-related targets were mined.Cytoscape software was used to construct a"component-target-disease"network.Gene ontology(GO)function and Kyoto encyclopedia of genes and genomes(KEGG)pathway enrichment analyses were carried out,and molecular docking of key components and targets was performed.Finally,further verification was conducted through in vivo experiment of rats.Result:A total of 39 effective components were identified in WXKL.These included 13 components derived from Panax notoginseng,15 components from Codonopsis pilosula,seven components from Glycyrrhizae Radix et Rhizoma,one component from Succinum,one component from Polygonatum odoratum,one component shared by both P.odoratum and C.pilosula,and one component shared by both Panax notoginseng and C.pilosula.Network pharmacology predicted that WXKL had 16 core antiarrhythmic targets and 79 related pathways,mainly involving adrenergic signaling in cardiomyocytes,cyclic guanosine monophosphate(cGMP)/protein kinase G(PKG),calcium signal,cyclic adenosine monophosphate(cAMP),interleukin(IL)-17,mitogen-activated protein kinase(MAPK),and tumor necrosis factor(TNF)signaling pathways.The results of in vivo experiment of rats showed that WXKL significantly improved the expression of β_(1)-adrenergic receptor(β_(1)-AR),cAMP,TNF-α,and calcium voltage-gated channel subunit alpha 1C(CACNA1C).Conclusion:WXKL can exert its antiarrhythmic effects through multiple components,multiple targets,and multiple pathways.This study prov

关 键 词：稳心颗粒 心律失常 细胞膜色谱 网络药理学 成分鉴定 

分 类 号：R284.2[医药卫生—中药学] R285[医药卫生—中医学] R289R287R22R2-031R33R24