基于整合药理学平台V2.0探讨痰瘀同治方抗心肌缺血再灌注损伤的分子机制  

Molecular Mechanism of Tanyu Tongzhi Formula in the Treatment of Myocardial Ischemia Reperfusion Injury Based on Integrative Pharmacology-Based Research Platform of Traditional Chinese Medicine V2.0

作　　者：高宏杰[1] 刘思鸿[1] 贡磊磊 张华敏[3] GAO Hongjie;LIU Sihong;GONG Leilei;ZHANG Huamin(Party Committee Office,Institute of Traditional Chinese Medicine Information,China Academy of Chinese Medical Sciences,Beijing 100700,China;Dept.of Pharmacy,Beijing Obstetrics and Gynecology Hospital,Capital Medical University,Beijing 100026,China;Institute of Chinese Materia Medica,China Academy of Chinese Medical Sciences,Beijing 100700,China)

机构地区：[1]中国中医科学院中医药信息研究所党委办公室,北京100700 [2]首都医科大学附属北京妇产医院药事部,北京100026 [3]中国中医科学院中药研究所,北京100700

出　　处：《中国医院用药评价与分析》2021年第3期273-277,共5页Evaluation and Analysis of Drug-use in Hospitals of China

基　　金：国家自然科学基金面上项目(No.81873199)。

摘　　要：目的:基于中医药整合药理学平台V2.0(TCMIP V2.0)探讨痰瘀同治方抗心肌缺血再灌注损伤(myocardial ischemia reperfusion injury,MIRI)的分子机制及其质量标志物。方法:利用TCMIP V2.0收集痰瘀同治方药物成分、靶标和MIRI疾病靶标,构建药物与疾病靶标互作网络,筛选药物和疾病共有靶标,并对共有靶标进行生物学过程分析,最后建立"成分-靶标-通路-药理作用"多维网络分析并对网络中的核心成分进行分析。结果:共收集痰瘀同治方中半夏、赤芍、川芎和甘草等药物化学成分157个,相应靶标272个,共收集获得MIRI疾病靶标290个。通过"中医药关联网络挖掘",对核心靶标中的前100个靶标进行分析,发现药物和疾病共有靶标31个,对共有靶标分析发现,共有靶标主要参与了血管生成的正调控、血管形成、自噬正调控、炎症反应和凋亡负调控等过程。京都基因与基因组百科全书通路富集分析结果显示,共有靶标主要富集于Fox O信号通路、缺氧诱导因子(HIF-1)信号通路、肿瘤坏死因子(TNF)信号通路、PI3K-Akt信号通路及血管内皮生长因子(VEGF)信号通路等信号通路。进一步对多维网络的分析发现,痰瘀同治方中46个成分通过与19个共有靶标作用影响上述5条信号通路发挥抗MIRI作用,其中槲皮素、山奈酚、柚皮素和黄芩素等成分通过干预AKT影响上述5条信号通路参与MIRI发生发展。结论:痰瘀同治方中槲皮素、山奈酚、柚皮素和黄芩素可通过调节炎症反应、自噬与凋亡、氧化应激及血管生成等过程抗MIRI。OBJECTIVE:To investigate the molecular mechanism of Tanyu Tongzhi formula in the treatment of myocardial ischemia reperfusion injury(MIRI)based on integrative pharmacology-based research platform of traditional Chinese medicine V2.0(TCMIP V2.0).METHODS:TCMIP V2.0 was used to collect drug components,targets and MIRI disease targets of Tanyu Tongzhi formula,and drug-disease target interaction network was established.Common targets of drug and disease were screened,and biological process of the common targets was analyzed.Eventually,multidimensional network analysis of"component-target-pathway-pharmacological action"was established and the core components in the network were analyzed.RESULTS:A total of 157 pharmaceutical chemical components were collected,including pinellia ternata,red peony root,Ligusticum wallichii and licorice,and 272 corresponding targets were identified.A total of 290 targets of MIRI were obtained.Through"Traditional Chinese Medicine Association Network Mining",the first 100 targets in the core targets were analyzed,and 31 targets for drugs and diseases were found.Common targets mainly participated into the positive regulation of angiogenesis,angiogenesis,positive regulation of autophagy,inflammatory response and negative regulation of apoptosis.Kyoto Encyclopedia of Genes and Genome Encyclopedia pathway enrichment analysis showed that the common targets were mainly enriched in FoxO,HIF-1,TNF,PI3 K-Akt and VEGF signaling pathways.Further multidimensional network analysis showed that 46 components in Tanyu Tongzhi formula affected the above 5 signaling pathways by acting with 19 common targets.Quercetin,kaempferol,naringenin and baicalein participated into the occurrence and development of MIRI through 5 signaling pathways by intervention of AKT.CONCLUSIONS:Quercetin,kaempferol,naringenin and baicalein in Tanyu Tongzhi formula can inhibit MIRI by regulating inflammatory response,autophagy and apoptosis,oxidative stress and angiogenesis.

关 键 词：痰瘀同治方 心肌缺血再灌注损伤 整合药理学 分子机制 

分 类 号：R932[医药卫生—生药学]