裴丽珊, 沈霞, 颜永刚, 张岗, 彭亮, 王艳霞, 平凡. 基于血管内皮生长因子信号通路/肿瘤坏死因子信号通路的桃核承气汤防治脑卒中双向调节分子网络机制J. 药学学报, 2020,55(5): 898-906. doi: 10.16438/j.0513-4870.2019-0867
引用本文: 裴丽珊, 沈霞, 颜永刚, 张岗, 彭亮, 王艳霞, 平凡. 基于血管内皮生长因子信号通路/肿瘤坏死因子信号通路的桃核承气汤防治脑卒中双向调节分子网络机制J. 药学学报, 2020,55(5): 898-906. doi: 10.16438/j.0513-4870.2019-0867
PEI Li-shan, SHEN Xia, YAN Yong-gang, ZHANG Gang, PENG Liang, WANG Yan-xia, PING Fan. The two-way regulation molecular network mechanism of Taohechengqi decoction in prevention and treatment of stroke based on vascular endothelial growth factor signaling pathway/tumor necrosis factor signaling pathwayJ. Acta Pharmaceutica Sinica, 2020,55(5): 898-906. doi: 10.16438/j.0513-4870.2019-0867
Citation: PEI Li-shan, SHEN Xia, YAN Yong-gang, ZHANG Gang, PENG Liang, WANG Yan-xia, PING Fan. The two-way regulation molecular network mechanism of Taohechengqi decoction in prevention and treatment of stroke based on vascular endothelial growth factor signaling pathway/tumor necrosis factor signaling pathwayJ. Acta Pharmaceutica Sinica, 2020,55(5): 898-906. doi: 10.16438/j.0513-4870.2019-0867

基于血管内皮生长因子信号通路/肿瘤坏死因子信号通路的桃核承气汤防治脑卒中双向调节分子网络机制

The two-way regulation molecular network mechanism of Taohechengqi decoction in prevention and treatment of stroke based on vascular endothelial growth factor signaling pathway/tumor necrosis factor signaling pathway

  • 摘要: 脑卒中长期以来损害着人类的健康,由于其发病机制复杂,目前尚无令人满意的治疗策略。桃核承气汤在临床上对脑卒中疗效显著。本研究通过TCMSP、TCMIP、BATMAN-TCM和TCMID数据库进行成分收集,采用PharmMapper、BATMAN-TCM数据库进行靶点的预测和筛选,使用R语言包clusterProfiler对靶点进行功能富集分析,最后应用GEO数据库和分子对接对关键靶点进行验证。结果显示,桃核承气汤51个活性成分可能通过调控内皮型一氧化氮合酶(NOS3)、环加氧酶2(PTGS2)和基质金属蛋白酶9(MMP9)等15个关键靶点,影响血管内皮生长因子信号通路等发挥预防脑卒中的作用,影响肿瘤坏死因子信号通路等发挥治疗脑卒中的作用。GEO数据分析表明,桃核承气汤防治脑卒中的关键靶点:雄激素受体(AR)、胱天蛋白酶8(CASP8)、细胞间黏附分子1(ICAM1)、白细胞介素1β(IL1B)、丝裂原活化蛋白激酶14(MAPK14)、MMP9、髓过氧化物酶(MPO)、过氧化物酶体增生激活受体γ(PPARG)、PTGS2和细胞肿瘤抗原p53(TP53)为上调基因;血清白蛋白(ALB)、雌激素受体1(ESR1)、NOS3、转录因子p65(RELA)和原癌基因络氨酸蛋白激酶Src(SRC)为下调基因。GEO分析说明,桃核承气汤可能通过下调ESR1、NOS3来预防脑卒中,通过上调ICAM1、IL1B、MAPK14、MMP9、PPARG、PTGS2和TP53,下调RELA、SRC来治疗脑卒中。本研究发现桃核承气汤在脑卒中防治过程中通过多基因和多途径发挥双向调节作用,为脑卒中治疗提供新的策略。

     

    Abstract: Stroke has been harmful to human health for a long time, and there is no satisfactory treatment strategy because of its complex pathogenesis. Taohechengqi decoction has been effective in the treatment of stroke. In this study, the components were collected by TCMSP, TCMIP, BATMAN-TCM and TCMID databases, the targets were predicted and screened by PharmMapper and BATMAN-TCM databases, and the functional enrichment analysis of the targets was carried out by using R language package clusterProfiler. Finally, the key targets are verified by GEO database and molecular docking. The results showed that 51 active components of Taohechengqi decoction may regulate 15 key targets such as nitric oxide synthase, endothelial (NOS3), prostaglandin G/H synthase 2 (PTGS2), matrix metalloproteinase-9 (MMP9), affecting vascular endothelial growth factor signaling pathway and other pathways to play a role in the prevention of stroke, affecting tumor necrosis factor signaling pathway and other pathways to play a role in the treatment of stroke. GEO data analysis showed that androgen receptor (AR), caspase-8 (CASP8), intercellular adhesion molecule 1 (ICAM1), interleukin-1 beta (IL1B), mitogen-activated protein kinase 14 (MAPK14), MMP9, myeloperoxidase (MPO), peroxisome proliferator-activated receptor gamma (PPARG), PTGS2 and cellular tumor antigen p53 (TP53) were up-regulated genes, while serum albumin (ALB), estrogen receptor 1 (ESR1), NOS3, transcription factor p65 (RELA) and proto-oncogene tyrosine-protein kinase Src (SRC) were down-regulated genes. GEO analysis explained that Taohechengqi decoction may prevent stroke by down-regulating ESR1, NOS3, and treat stroke by up-regulating ICAM1, IL1B, MAPK14, MMP9, PPARG, PTGS2, TP53, and down-regulating RELA and SRC. The study found that in the process of prevention and treatment of stroke, Taohechengqi decoction played a two-way regulation role through multi-genes and multiple ways, which provided a new strategy for the treatment of stroke.

     

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