基于网络药理学方法和分子对接技术探讨芪红通脑合剂治疗气虚血瘀型急性脑梗死的作用机制  

The action mechanism of the Qihong Tongnao mixture on acute cerebral infarction of the Qi deficiency and blood stasis type based on network pharmacology and molecular docking

作　　者：吴金灿 李世举[1] 吴松鹰 王艳旭[3] 张蔚 周明星 张天石 施方圆 陈昕怡 梁睿忻 WU Jincan

机构地区：[1]福建中医药大学附属第二人民医院,福建福州350003 [2]福建省中医药科学院,福建福州350003 [3]福建中医药大学附属人民医院,福建福州350004 [4]福建中医药大学附属康复医院,福建福州350003

出　　处：《中医临床研究》2024年第35期53-60,共8页Clinical Journal Of Chinese Medicine

基　　金：福建省自然科学基金项目(2022J01826)。

摘　　要：目的:通过网络药理学和分子对接技术预测芪红通脑合剂治疗急性脑梗死的作用靶点和分子机制。方法:依托中药系统药理学数据库与分析平台预测芪红通脑合剂活性成分和药物潜在靶点,从GeneCards数据库中检索到急性脑梗死疾病潜在靶点。取药物靶点和疾病靶点的交集,以获取芪红通脑合剂抗急性脑梗死的潜在作用靶点。通过基因本体论(GO)功能富集分析和京都基因与基因组百科全书(KEGG)通路富集分析筛选潜在靶点中的核心靶点。从RCSB PDB数据库下载关键靶点蛋白的晶体构象,进行分子对接和可视化处理。结果:预测芪红通脑合剂有12种有效活性成分及35个疾病相关潜在靶点,关键成分为槲皮素、β-谷甾醇、芒柄花黄素、杨梅酮、木樨草素等,作用于C-C基序趋化因子配体2(C-C Motif Chemokine Ligand 2,CCL2)、白细胞介素(Interleukin,IL)-1β、IL-6、人纤溶酶原激活物抑制因子1(Plasminogen Activator Inhibitor 1,SERPINE1)和肿瘤坏死因子(Tumor Necrosis Factor,TNF)这5个核心靶点。GO分析揭示了该药物可能主要通过对外部刺激反应的正向调节、细胞对脂多糖的反应、上皮细胞凋亡过程、对细菌来源分子的反应、伤口愈合等多种生物过程发挥作用。KEGG揭示了芪红通脑合剂可能通过晚期糖基化终末产物(Advanced Glycation End Products,AGE)-晚期糖基化终末产物受体(Advanced Glycation End Product Receptor,RAGE)信号通路、流体剪应力与动脉粥样硬化、脂质与动脉粥样硬化、IL-17信号通路等潜在通路发挥治疗急性脑梗死的作用。分子对接结果提示5个关键靶点与核心活性成分有良好的结合能力。结论:芪红通脑合剂可能通过抗炎、改变血液流变学达到治疗急性脑梗死的目的。Objective:To predict the targets and molecular mechanisms of the Qihong Tongnao mixture(芪红通脑合剂)in the treatment of acute cerebral infarction(ACI)through network pharmacology and molecular docking techniques.Methods:The active ingredients and potential targets of the Qihong Tongnao mixture were predicted by TCMSP,and potential targets of ACI were retrieved from the GeneCards database.The intersection of medicine targets and disease targets were taken to obtain the potential target of the Qihong Tongnao mixture for anti-ACI.The core targets of potential targets were screened through GO functional enrichment analysis and KEGG pathway enrichment analysis.Finally,the crystal conformation of key target proteins was downloaded from the RCSB PDB database for molecular docking and visualization processing.Results:It was predicted that the Qihong Tongnao mixture had 12 effective active ingredients and 35 potential disease-related targets,with key ingredients such as quercetin,β-sitosterol,formononetin,myricetin and luteolin,which acted on five core targets:CCL2,IL-1β,IL-6,SERPINE1 and TNF.The GO enrichment analysis revealed that the Qihong Tongnao mixture might mainly exert its effects through regulating the positive regulation of response to external stimuli,cell response to lipopolysaccharides,epithelial cell apoptosis process,response to bacterial derived molecules,wound healing and other biological processes.The KEGG enrichment analysis revealed that the Qihong Tongnao mixture might play a role in treating ACI through AGE-RAGE signaling pathway,fluid shear stress and atherosclerosis,lipid and atherosclerosis,IL-17 signaling pathway and other potential pathways.The molecular docking results indicated that five key targets had good binding ability with the core active ingredients.Conclusion:The Qihong Tongnao mixture may achieve the goals of treating ACI by anti-inflammatory and altering hemorheology.

关 键 词：急性脑梗死 芪红通脑合剂 网络药理学 分子对接 机制研究 

分 类 号：R743.33[医药卫生—神经病学与精神病学]