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作 者:郑雅 严石焕 覃杨[3] 蓝慧琴 王博龙 朱丹 ZHENG Ya;YAN Shihuan;QIN Yang;LAN Huiqin;WANG Bolong;ZHU Dan(Affiliated Hospital of Hebei University,Baoding 071000 Hebei,China;Yichun University,Yichun 336000 Jiangxi,China;College of Pharmacy,Guangxi Medical University,Nanning 530213 Guangxi,China)
机构地区:[1]河北大学附属医院,河北保定071000 [2]宜春学院,江西宜春336000 [3]广西医科大学药学院,广西南宁530213
出 处:《中药新药与临床药理》2021年第4期526-532,共7页Traditional Chinese Drug Research and Clinical Pharmacology
基 金:广西自然科学基金青年基金项目(2013GXNSFBA019150);广西高校中青年教师基础能力提升项目(2018KY0136);广西一流学科(药学)建设项目(GXFCDP-PS-2018)。
摘 要:目的基于入血成分研究鹿角方治疗慢性心力衰竭(chronic heart failure,CHF)的机制。方法依托TCMSP数据库和SwissTarget Prediction数据平台预测鹿角方入血成分靶点。运用DisGeNET、TTD、GrugBank疾病数据库挖掘作用于慢性心力衰竭的靶点,将其与鹿角方活性成分靶点相互映射,筛选出共同靶点。应用STRING平台构建靶蛋白相互作用网络,运用Cytoscape软件中的cytoHubba插件分析关键子网络。利用Omicshare平台对筛选出来的靶点进行GO功能富集和KEGG通路分析。结果鹿角方入血成分靶点中与慢性心力衰竭相关的共有37个,它们参与血液循环、血管直径的调节、血压调节、细胞增殖调控等生物过程;调控c GMP-PKG信号通路、钙信号通路、血管平滑肌收缩信号通路、VEGF信号通路、松弛素信号通路、流体剪切应力和动脉粥样硬化、心肌细胞肾上腺素能信号通路、IL-17信号通路、AGE-RAGE信号通路、TRP通道的炎症介质调节、雌激素、甲状旁腺激素合成、分泌及作用,以及胰岛素抵抗等通路。结论多靶点、多通路调控心血管、抑制炎症、调节激素是鹿角方治疗慢性心力衰竭的主要机理,PRKCA及松弛素信号通路可能是其关键靶点及通路。Objective The mechanism of Lujiao prescription in the treatment of chronic heart failure was studied based on the absorbed components in plasma. Methods TCMSP database and SwissTarget Prediction data platform were used to predict the targets of absorbed component in plasma of Lujiao prescription. DisGeNET, TTD and GrugBank disease databases were used to mine the targets of chronic heart failure,which were mapped with targets of active ingredients in Lujiao prescription to screen out common targets. The STRING platform was used to construct the targets protein interaction network, and cytoHubba was used to analyze the key subnetworks. The Omicshare platform was used to carry out GO function enrichment and KEGG pathway analysis on the selected targets. Results Among the component targets in plasma of Lujiao prescription,there are 37 targets related to chronic heart failure.They are involved in biological processes such as blood circulation,regulation of blood vessel diameter,regulation of blood pressure and regulation of cell proliferation. The components in plasma of Lujiao prescription regulate the cGMP-PKG signaling pathway,calcium signaling pathway,signaling pathway involved in vascular smooth muscle contraction,VEGF signaling pathway,relaxin signaling pathway,fluid shear stress and atherosclerosis,adrenergic signaling pathway in myocardial cell, IL-17 signaling pathway, AGE-RAGE signaling pathway in diabetic complications, inflammatory mediators regulation of TRP channels, estrogen signaling pathway, parathyroid hormone synthesis,secretion and action,and insulin resistance and other signal pathways. Conclusion Multi-target and multi-pathway regulation of cardiovascular system,inhibition of inflammation and regulation of hormones are the main mechanisms of Lujiao prescription in the treatment of chronic heart failure, PRKCA and relaxin signaling pathway may be the key targets and pathways.
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