目的:探究当归四逆加吴茱萸生姜汤调节雷诺病的系统药理学机制,筛选先导化合物。方法:基于中药系统药理学数据库与分析平台(traditional Chinese medicine systems pharmacology, TCMSP)和Cytoscape 3.6分析软件,构建当归四逆加吴茱萸...目的:探究当归四逆加吴茱萸生姜汤调节雷诺病的系统药理学机制,筛选先导化合物。方法:基于中药系统药理学数据库与分析平台(traditional Chinese medicine systems pharmacology, TCMSP)和Cytoscape 3.6分析软件,构建当归四逆加吴茱萸生姜汤的“中药-成分-靶点”调控网络,对本方调节靶点进行通路富集分析,综合使用系统药理学和计算机辅助药物设计的方法,筛选本方的潜在活性成分。结果:本方初步筛选出696个化合物成分,获得401个特异性靶点,形成“化合物-靶点”5 446调控对。本方调节靶点基因本体(gene ontology, GO)富集通路包括氨基酸结合、G蛋白偶联受体活性等生物学过程及线粒体基质、线粒体等细胞组分相关,受预激抑制、谷胱甘肽代谢过程、抑制性突触后电位等分子功能影响;京都基因与基因组百科全书(kyoto encyclopedia of genes and genomes, KEGG)富集包括HIF-1信号通路、cAMP信号通路、IL-17信号通路等。分子对接和药效团筛选得出化合物(-)-Medicocarpin具有较好的潜在治疗作用。结论:当归四逆加吴茱萸生姜汤可能通过调节HIF-1信号通路、cAMP信号通路、IL-17信号通路等改善雷诺病;甘草中的(-)-Medicocarpi、Yinyanghuo D与吴茱萸中的Goshuyuamide II等可以作为治疗雷诺病的潜在有效成分。展开更多
A canine model of ischemic ventricular tachyarrhythmias was established in open-chest dogs subjected to programmed electrical stimulation (PES) for 5 ̄8 days after acute myocardial infarction. The electrophysiologic e...A canine model of ischemic ventricular tachyarrhythmias was established in open-chest dogs subjected to programmed electrical stimulation (PES) for 5 ̄8 days after acute myocardial infarction. The electrophysiologic effects of sophoridine (Sop) and procainamide (PA) were observed in this canine model. With routine methods of PES, ventricular tachycardia (VT) and ventricular fibrilation (VF) could be reproducibly initiated in this model. Both drugs distinctly lengthened the QTc interval ( P <0.01) and the effective refractory period (ERP) in normal and ischemic ventricular myocardium ( P <0.01), decreased the dispersion of ERP in ischemic myocardium and the dispersion of ERP in left ventricle (P <0.05), and increased the diastolic excitability threshold of normal and ischemic ventricular myocardium remarkably ( P <0.01). Both drugs effectively prevented the PES-induced VT or VF and ischemia-induced VF ( P <0.05). The results indicated that this canine model is a good and reliable one, sophoridine and procainamide may be effective in preventing the onset of reentrant ventricular tachyarrhythmias after myocardial ischemic damage.展开更多
文摘目的:探究当归四逆加吴茱萸生姜汤调节雷诺病的系统药理学机制,筛选先导化合物。方法:基于中药系统药理学数据库与分析平台(traditional Chinese medicine systems pharmacology, TCMSP)和Cytoscape 3.6分析软件,构建当归四逆加吴茱萸生姜汤的“中药-成分-靶点”调控网络,对本方调节靶点进行通路富集分析,综合使用系统药理学和计算机辅助药物设计的方法,筛选本方的潜在活性成分。结果:本方初步筛选出696个化合物成分,获得401个特异性靶点,形成“化合物-靶点”5 446调控对。本方调节靶点基因本体(gene ontology, GO)富集通路包括氨基酸结合、G蛋白偶联受体活性等生物学过程及线粒体基质、线粒体等细胞组分相关,受预激抑制、谷胱甘肽代谢过程、抑制性突触后电位等分子功能影响;京都基因与基因组百科全书(kyoto encyclopedia of genes and genomes, KEGG)富集包括HIF-1信号通路、cAMP信号通路、IL-17信号通路等。分子对接和药效团筛选得出化合物(-)-Medicocarpin具有较好的潜在治疗作用。结论:当归四逆加吴茱萸生姜汤可能通过调节HIF-1信号通路、cAMP信号通路、IL-17信号通路等改善雷诺病;甘草中的(-)-Medicocarpi、Yinyanghuo D与吴茱萸中的Goshuyuamide II等可以作为治疗雷诺病的潜在有效成分。
文摘A canine model of ischemic ventricular tachyarrhythmias was established in open-chest dogs subjected to programmed electrical stimulation (PES) for 5 ̄8 days after acute myocardial infarction. The electrophysiologic effects of sophoridine (Sop) and procainamide (PA) were observed in this canine model. With routine methods of PES, ventricular tachycardia (VT) and ventricular fibrilation (VF) could be reproducibly initiated in this model. Both drugs distinctly lengthened the QTc interval ( P <0.01) and the effective refractory period (ERP) in normal and ischemic ventricular myocardium ( P <0.01), decreased the dispersion of ERP in ischemic myocardium and the dispersion of ERP in left ventricle (P <0.05), and increased the diastolic excitability threshold of normal and ischemic ventricular myocardium remarkably ( P <0.01). Both drugs effectively prevented the PES-induced VT or VF and ischemia-induced VF ( P <0.05). The results indicated that this canine model is a good and reliable one, sophoridine and procainamide may be effective in preventing the onset of reentrant ventricular tachyarrhythmias after myocardial ischemic damage.