摘要
目的 从分子水平探究交泰丸治疗心律失常的作用机制。方法 (1)采用中医药整合药理学研究平台(Integrative Pharmacology-based Research Platform of Traditional Chinese Medicine,TCMIP)V2.0,检索并获取黄连和肉桂活性成分、靶标,以及心律失常疾病和证候靶标信息,借助平台构建“中药-证素-疾病-靶标-通路”多维网络,获得药物干预疾病的关键靶标,通过基因本体数据库(Gene Ontology,GO)和京都基因与基因组百科全书库(Kyoto Encyclopaedia of Genes and Genomes,KEGG)进行富集分析,预测交泰丸治疗心律失常的分子机制。(2)选取雄性SD大鼠32只,随机分为对照组(N)、模型组(M)、交泰丸组(J)、阳性药组(Meto)4组,以尾静脉推注肾上腺素(Epi)制造心律失常模型,利用酶联免疫吸附法(ELISA)观察各组大鼠血浆血管紧张素Ⅱ(AngⅡ)、儿茶酚抑素(CST)、神经肽Y(NPY)的含量。结果 (1)交泰丸共筛选出23个活性成分(黄连14个,肉桂9个),心律失常相关靶标850个。这些活性成分通过调控基因表达的正调控、丝裂原活化蛋白激酶(mitogen-activated protein kinase,MAPK)级联激活、信号识别颗粒(signal recognition particle,SRP)依赖的共翻译蛋白靶向膜、细胞因子介导的信号通路、调节心室心肌细胞动作电位、通过心脏传导调节心率等生物过程,直接或间接参与促红细胞生成素激活肾素-血管紧张素系统(RAS)、加速纤维肉瘤蛋白(rapidly accelerated fibrosarcoma,RAF)激活等信号通路,从而发挥抗心律失常的作用。(2)模型组大鼠血浆AngⅡ、CST、NPY含量明显高于对照组(P<0.01),交泰丸组AngⅡ、CST、NPY水平与模型组比较明显下降(P<0.05或P<0.01),且交泰丸组疗效优于阳性药组。结论 通过整合药理学策略结合药效验证,揭示了交泰丸多途径抗心律失常作用的分子机制,验证了RAS系统与交感神经活性在心律失常中的重要作用,并明确交泰丸对心律失常有一定的调节作�
Objective To explore the anti-arrhythmia mechanism of Jiaotai pill at the molecular level.Methods(1)The Integrative Pharmacology-based Research Platform of Traditional Chinese Medicine(TCMIP) V2.0 was used to retrieve and obtain information on the active ingredients and targets of coptidis and cinnamon, as well as target information of arrhythmias and their syndromes. With the help of the Platform, the multi-dimensional network of "TCM-syndrome-disease-target-pathway" was constructed to obtain the key targets for drug intervention in diseases. Gene Ontology(GO) database and Kyoto Encyclopaedia of Genes and Genomes(KEGG) were used for enrichment analysis to predict the molecular mechanism of Jiaotai pill in the treatment of arrhythmia.(2)32 male SD rats were randomly divided into four groups: control group(N), model group(M), Jiaotai pill group(J) and positive drug group(Meto). The arrhythmia model was made by epinephrine injection through tail vein. Enzyme linked immunosorbent assay(ELISA) was used to observe the contents of angiotensin Ⅱ(AngⅡ), catecholstatin(CST) and neuropeptide Y(NPY) in plasma of rats.Results(1)A total of 23 active components(14 from coptidis, 9 from cinnamon) were screened out in Jiaotai pill. 850 arrhythmiarelated targets were selected. These active ingredients jointly regulate biological processes such as positive regulation of gene expression, mitogen-activated protein kinase(MAPK) cascading activation, signal recognition particle(SRP)dependent cotranslational protein targeting membrane, cytokine-mediated signaling pathways, regulation of ventricular cardiomyocyte action potential, and heart rate regulation through cardiac conduction, directly or indirectly participate in erythropoietin activation of renin angiotensin system(RAS) signaling pathways, rapidly accelerated fibrosarcoma(RAF)activation signaling pathways, etc., and thus played an anti-arrhythmia effect.(2)The contents of AngⅡ, CST and NPY in plasma in the model group were significantly higher than those in the control gr
作者
陈金红
刘志超
樊博雅
梁嘉钰
邓芳隽
李晓凤
丛紫东
杜武勋
Chen Jinhong;Liu Zhichao;Fan Boya;Liang Jiayu;Deng Fangjun;Li Xiaofeng;Cong Zidong;Du Wuxun(School of Rehabilitation Medicine,Weifang Medical University,Shandong,261053,China;Graduate School of Tianjin University of Traditional Chinese Medicine,Tianjin 301617,China;The Second Affiliated Hospital of Tianjin University of TCM,Tianjin 300150,China)
出处
《世界科学技术-中医药现代化》
CSCD
北大核心
2022年第5期1993-2002,共10页
Modernization of Traditional Chinese Medicine and Materia Medica-World Science and Technology
基金
国家自然科学基金委员会青年科学基金项目(82004329):基于细胞膜色谱和组分中药的稳心颗粒治疗心律失常药效物质基础和作用机制研究,负责人:李晓凤
天津市教育委员会人文社科项目(2019SK025):基于《黄帝内经》运气九篇注释的五运六气理论基础研究,负责人:李晓凤。
