基于网络药理学和体外实验探讨丹参-川芎药对治疗动脉粥样硬化的作用机制  

Mechanism of Danshen(丹参)-Chuanxiong(川芎)Medicinal Pair in the Treatment of Atherosclerosis Based on Network Pharmacology and In Vitro Experiment

作　　者：王钰莹 王川[1] 胡锐[1] 刘继平[1] 王斌[1] 卫昊[1] 张珍 Wang Yuying;Wang Chuan;Hu Rui;Liu Jiping;Wang Bin;Wei Hao;Zhang Zhen(Department of Pharmacology,Shaanxi University of Chinese Medicine/Key Laboratory of Pharmacodynamics and Material Basis of Chinese Medicine of Shaanxi Administration of Traditional Chinese Medicine,Key Laboratory of Traditional Chinese Medicine Basic and New Drug Research of Shaanxi Province,Xiaoyang 712046;Shaanxi Traditional Chinese Medicine Resources Industrialization Collaborative Innovation Center,Xiaoyang 712083)

机构地区：[1]陕西中医药大学药理教研室/陕西省中医药管理局中药药效机制与物质基础重点研究室/陕西省中药基础与新药研究重点实验室,咸阳712046 [2]陕西省中药资源产业化协同创新中心,咸阳712083

出　　处：《中药药理与临床》2022年第4期67-73,共7页Pharmacology and Clinics of Chinese Materia Medica

基　　金：国家自然科学基金项目(编号:81800401);陕西省科技厅科技计划项目(编号:2021SF-368、2022SF-435、2022SF-207);大学生创新创业训练计划项目(编号:S202010716021);陕西中医药大学学科创新团队项目(编号:2019-YL13)。

摘　　要：目的:基于网络药理学和体外实验探讨丹参-川芎治疗动脉粥样硬化的主要化学成分及其作用机制。方法:TCMSP数据库筛选并收集丹参-川芎的化学成分及其对应靶标,使用Cytoscape 3.7.2软件绘制药物-活性成分-交集靶点网络图,利用Metascape数据库对丹参-川芎治疗动脉粥样硬化的潜在作用靶标进行GO分类富集分析和KEGG通路富集分析。使用UCSF CHIMERA软件进行分子对接,选择最佳的结合靶点。通过细胞实验验证丹参-川芎药对的抗动脉粥样硬化作用。结果:从丹参-川芎中共得到72个候选活性成分,包括木犀草素、丹参酮IIA、二氢丹参内酯、杨梅酮、丹参新醌等,与动脉粥样硬化相关的潜在作用靶标67个,包括AKT1、IL6、VEGFA、MAPK1、TP53等,主要的信号通路有癌症通路、PI3K-AKT信号通路、流体剪切应力与动脉粥样硬化通路、JAK-STAT信号通路、炎症性肠病、NF-κB信号通路、脂肪细胞脂解的调节等信号通路。细胞实验结果表明,丹参-川芎药对可减少巨噬细胞的泡沫化,降低AKT1、ERK1/2蛋白的磷酸化水平,抑制VEGFA的蛋白表达发挥抗动脉粥样硬化作用。结论:丹参-川芎治疗动脉粥样硬化具有多靶点、多通路的特点,其机制可能与调控AKT1、ERK1/2、VEGFA的蛋白表达有关。Objective:To explore the main components and mechanism of Danshen-Chuanxiong medicinal pair in the treatment of atherosclerosis based on network pharmacology and in vitro experiment. Methods:Traditional Chinese Medicinal Systems Pharmacology Database and Analysis Platform(TCMSP) was used to screen and collect the chemical components of Danshen-Chuanxiong medicinal pair and the corresponding targets, and Cytoscape 3.7.2 was used to draw a drug-active component-target network. Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment analyses were carried out by Metascape to analyze the potential targets of Danshen-Chuanxiong medicinal pair in the treatment of atherosclerosis. UCSF Chimera was applied for molecular docking to select the optimal binding targets. The anti-atherosclerotic effect of Danshen-Chuanxiong medicinal pair was verified through the cellular experiment. Results:Seventy-two active component candidates, including luteolin, tanshinone IIA,dihydrotanshinlactone, myricetin, and neotanshinone, were obtained from Danshen-Chuanxiong medicinal pair. Sixty-seven potential targets related to atherosclerosis, including protein kinase B1(AKT1),interleukin-6(IL-6),vascular endothelial growth factor A(VEGFA),mitogen-activated protein kinase 1(MAPK1),and tumor protein p53(TP53),were obtained. The main signaling pathways involved cancer, phosphoinositide 3 kinase-protein kinase B(PI3 K-AKT),shear stress and atherosclerosis, Janus kinase-signal transducer and activator of transcription protein(JAK-STAT),inflammatory bowel disease, nuclear factor kappa B(NF-κB),regulation of adipocyte lipolysis, etc. The results of the cellular experiment showed that Danshen-Chuanxiong medicinal pair could play an anti-atherosclerotic role by decreasing the macrophage foaming, reducing the phosphorylation level of AKT1 and extracellular signal-regulated kinase 1/2(ERK1/2) proteins, and inhibiting the expression of VEGFA protein. Conclusion:Danshen-Chuanxiong medicinal pair has multi-target and multi-pathway

关 键 词：丹参 川芎 药对 动脉粥样硬化 蛋白激酶 血管内皮生长因子A 细胞外调节蛋白激酶 

分 类 号：R285.6[医药卫生—中药学]