基于网络药理学探讨丹皮-赤芍药对治疗脓毒症的作用机制  

Study on the mechanism of Danpi-Chishao in the treatment of sepsis based on network pharmacology

作　　者：苏家卉 吴彩军 南富耀 夏欢 任阳 马林沁 Su Jiahui;Wu Caijun;Nan Fuyao;Xia Huan;Ren Yang;Ma Linqin(Dongzhimen Hospital,Beijing University of Chinese Medicine,Beijing 100700,China;Beijing University of Chinese Medicine,Beijing 100105,China;Department of Emergency,Dongzhimen Hospital,Beijing University of Chinese Medicine,Beijing 100700,China;Institute of Sepsis,Beijing University of Chinese Medicine,Beijing 100700,China)

机构地区：[1]北京中医药大学东直门医院,北京100700 [2]北京中医药大学,北京100105 [3]北京中医药大学东直门医院急诊科,北京100700 [4]北京中医药大学脓毒症研究所,北京100700

出　　处：《中国医师杂志》2023年第2期178-185,共8页Journal of Chinese Physician

基　　金：国家重点研发计划(2021YFC1712901),国家科技重大专项(601209)。

摘　　要：目的基于网络药理学方法验证丹皮-赤芍药对治疗脓毒症的作用机制。方法在TCMSP、OMIM、GeneCards等数据库中检索丹皮-赤芍、脓毒症对应靶点,用Cytoscape 3.8.2软件构建"中药材-活性成分-靶点-疾病"分析图,DAVID数据库进行基因本体(GO)与京都基因与基因组百科全书(KEGG)功能富集分析,微生信云平台绘制气泡图。结果丹皮-赤芍药对共有36个有效成分,主要为槲皮素、山奈酚、黄芩苷、β-谷甾醇、豆甾醇、芍药苷等。与脓毒症潜在共有关键靶点96个,其中度值>4.9者为前列腺素G/H合酶2(PTGS2)、转录因子p65(RELA)、磷酸肌醇3激酶(PIK3CG)、细胞凋亡调节因子(BAX)、细胞凋亡调节因子(BCL2)、半胱天冬酶-3(CASP3)。蛋白相互作用(PPI)网络分析结果共有10个重要靶标蛋白,包括RAC-α丝氨酸/苏氨酸蛋白激酶(AKT1)、白介素-6(IL-6)、肿瘤坏死因子(TNF)、白介素-1β(IL-1β)、血管内皮生长因子A(VEGFA)、细胞肿瘤抗原p53(TP53)、基质金属蛋白酶-9(MMP9)、CASP3、PTGS2、人超敏C-C趋化因子2(CCL2)。富集分析提示主要信号通路包括脂质与动脉粥样硬化通路、AGE-RAGE信号通路、癌症通路、肿瘤坏死因子信号通路、HIF-1信号通路、IL-17信号通路等。结论丹皮-赤芍药对可能通过活性成分槲皮素、山奈酚、芍药苷等,作用于PTGS2、RELA、PIK3CG、BAX、BCL2、CASP3等靶蛋白,通过TNF相关信号通路、HIF-1信号通路、IL-17信号通路等产生对脓毒症的干预效应;但尚需进一步实验验证。Objective To analyze the mechanism of Danpi-Chishao in treatment of sepsis based on network pharmacology.Methods The corresponding targets of Danpi-Chishao and sepsis were carried out through TCMSP database,OMIM database and Genecards database.Cystoscope 3.8.2 software was used to construct the"Chinese medicine-active components-target-disease"network diagram.Gene ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis were carried out by DAVID database.Weisheng cloud platform was used to draw bubble map.Results A total of 36 effective components of Danpi-Chishao was obtained,mainly including quercetin,kaempferol,baicalin,β-sitosterol,stigmasterol,paeoniflorin and so on.There were 96 potential common key targets between Danpi-Chishao and sepsis,such as prostaglandin-endoperoxide synthase 2(PTGS2),transcription factor p65(RELA),phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit gamma(PIK3CG),B-cell lymphoma 2(BCL-2)-associated X(BAX),BCL-2,Caspase-3(CASP3)with a degree value>4.9.The result of protein-protein interaction(PPI)network analysis showed that there were 10 important target proteins,including alpha serine/threonine-protein kinase(AKT1),interleukin-6(IL-6),tumor necrosis factor(TNF),interleukin-1β(IL-1β),vascular endothelial growth factor A(VEGFA),cellular tumor antigen p53(TP53),matrix metalloproteinase-9(MMP9),CASP3,PTGS2,C-C motif chemokine ligand 2(CCL2).The pathways obtained by GO and KEGG enrichment analysis included atherosclerosis pathway,advanced glycation end products(AGE)-receptor for advanced glycation end products(RAGE)signal pathway,cancer pathway,tumor necrosis factor signal pathway,hypoxia-inducible factor(HIF)signal pathway,IL-17 signal pathway and other pathway.Conclusions The mechanism of the intervention effect of Danpi-Chishao on sepsis may be that the active components such as quercetin,kaempferol,paeoniflorin act on target proteins such as PTGS2,RELA,PIK3CG,BAX,BCL2,CASP3,and through TNF-related signal pathway,HIF-1 signal pathway,IL-17 signa

关 键 词：脓毒症 赤芍 丹皮 网络药理学 

分 类 号：R285[医药卫生—中药学]