基于网络药理学和体外实验探讨附子-干姜抗心肌缺血再灌注损伤的作用机制  

Study on the mechanism of Aconiti Lateralis Radix Preparata-Zingiberis Rhizoma in treating myocardial ischemia-reperfusion injury based on network pharmacology and experimental verification

作　　者：谢锋 段广靖 李敏[2] 兰卫[1] XIE Feng;DUAN Guang-jing;LI Min;LAN Wei(School of Chinese Medicine,Xinjiang Medical University,Urumqi 830000,China;School of Pharmacy,Shaanxi University of Chinese Medicine,Xianyang 712046,China)

机构地区：[1]新疆医科大学中医学院,乌鲁木齐830000 [2]陕西中医药大学药学院,咸阳712046

出　　处：《天然产物研究与开发》2023年第1期151-158,共8页Natural Product Research and Development

基　　金：国家自然科学基金(81373988);新疆医科大学博士基金目(2019-1);国家重点研发计划(2017YFC1703901-3);国家重点研发计划(2017YFC1703902-3)。

摘　　要：运用网络药理学方法探讨附子-干姜(Aconiti Lateralis Radix Preparata-Zingiberis Rhizoma,AZ)抗心肌缺血再灌注损伤(myocardial ischemia-reperfusion injury,MI/RI)的潜在机制。通过中药系统药理数据库TCMSP筛选AZ的活性成分;Disgenet数据库获得MI/RI靶点;STITCH数据库获得蛋白互作;用DAVID数据库获得GO功能富集与KEGG信号通路并利用Cytoscape 3.8.0进行绘图;细胞实验验证网络药理学预测的结果。结果共获得AZ活性成分16个、治疗靶点171个;作图分析发现AKT1、IL6、TNF为潜在靶点;GO富集分析发现AZ可能通过凋亡、炎症、血管舒张发挥治疗作用;KEGG分析发现AZ可能通过PI3K-AKT信号通路、TNF信号通路、HIF信号通路发挥治疗作用;体外研究发AZ可使缺氧复氧损伤的大鼠血管内皮细胞存活率提高、降低凋亡率、氧化损伤;提高HIF-α、VEGF、eNOS蛋白的表达。附子-干姜激活HIF/VEGF/eNOS信号通路,降低血管内皮细胞氧化损伤、凋亡率发挥抗心肌缺血再灌注损伤的作用。To explore the mechanism of Aconiti Lateralis Radix Preparata-Zingiberis Rhizome(AZ)against myocardial ischemia-reperfusion injury(MI/RI)by network pharmacology.To search the active components and corresponding targets of AZ through the TCMSP databases.MI/RI targets were obtained from Disgenet database.Constructed protein interaction network map by String online database.At the same time GO and KEGG enrichment analysis of key targets were carried out by using R language.The results of network pharmacologic prediction were verified by cell experiments.A total of 16 AZ active compounds and 171 targets were obtained.GO analysis showed that AZ may play a role in the treatment of MI/RI through apoptosis,inflammation and vasodilation.KEGG analysis showed that AZ may play a therapeutic role through PI3K-Akt signaling pathway,TNF signaling pathway and HIF signaling pathway.Experimental verification showed that AZ could improve the survival rate of vascular endothelial cells,reduce the apoptosis rate and oxidative damage of rats with hypoxia reoxygenation injury.Moreover,the expression of HIF-α,VEGF and eNOS protein was increased.AZ treatment of MI/RI can reduce the oxidative damage and apoptosis rate of vascular endothelial cells by activating the HIF/VEGF/eNOS signaling pathway.

关 键 词：网络药理学 附子-干姜 血管舒张 心肌缺血再灌注损伤 

分 类 号：R285.5[医药卫生—中药学]