基于网络药理学及分子对接探究银杏叶干预糖尿病心肌病的作用机制

The mechanism of gingko leaf intervention in diabetic cardiomyopathy based on network pharmacology and molecular docking

目的:使用网络药理学的方法研究银杏叶治疗糖尿病心肌病的机制。方法:在中药系统药理学数据库与分析平台(TCMSP)检索银杏叶的主要成分,通过GeneCard、OMIM、Disgenet数据库筛选糖尿病心肌病的潜在靶点,利用韦恩图获取银杏叶与糖尿病心肌病的共同靶点,导入STRING蛋白互作平台建构PPI互作网络图,用Cytoscape软件将互作图进行拓扑学分析,并筛选出核心交集靶点。使用DAVID在线数据库对交集靶点进行GO与KEGG富集分析。最后对筛选得到的部分关键靶点及其对应化合物进行分子对接,进一步验证银杏叶干预糖尿病心肌病的核心作用靶点。结果:银杏叶与糖尿病心肌病共有91个交集靶点,通过拓扑学分析发现蛋白激酶B1(Akt1)、肿瘤坏死因子(TNF)、白细胞介素-6(IL-6)、血管内皮生长因子A(VEGFA)、白细胞介素-1β(IL-1β)是银杏叶治疗糖尿病心肌病的核心靶点。KEGG通路富集分析结果显示,银杏叶作用于糖尿病心肌病的通路涉及糖尿病并发症中AGEs-RAGE信号通路、脂质与动脉粥样硬化、IL-17信号通路、TNF信号通路、HIF-1信号通路等。结论:银杏叶可能通过作用于Akt1、TNF、IL-6、VEGFA、IL-1β等靶点减轻炎症和氧化应激水平,抑制心肌细胞凋亡。

Objective:To study the mechanism of ginkgo leaf in the treatment of diabetic cardiomyopathy by network pharmacology.Methods:The main components of ginkgo leaf were searched in the Traditional Chinese Medicine Pharmacology Database and Analysis Platform(TCMSP),and the potential targets of diabetic cardiomyopathy were screened by GeneCard,OMIM and Disgenet databases.The common targets of ginkgo leaf and diabetic cardiomyopathy were obtained by Venn diagram.The STRING protein interaction platform was imported to construct the PPI interaction network diagram.Topological analysis was carried out on the interaction diagram using Cytoscape software,and core intersection targets were screened.GO and KEGG enrichment analysis of intersection targets was performed using DAVID online database.Finally,molecular docking of some key targets and their corresponding compounds was performed to further verify the core target of ginkgo leaf in the intervention of diabetic cardiomyopathy.Results:There were 91 intersection targets between ginkgo leaf and diabetic cardiomyopathy.Topological analysis showed that protein kinase B1(Akt1),tumor necrosis factor(TNF),interleukin-6(IL-6),vascular endothelial growth factor A(VEGFA)and interleukin-1beta(IL-1β)were the core targets of ginkgo leaf in the treatment of diabetic cardiomyopathy.KEGG pathway enrichment analysis showed that the pathway of ginkgo leaf on diabetic cardiomyopathy involved AGEs-RAGE signaling pathway,lipid and atherosclerosis,IL-17 signaling pathway,TNF signaling pathway,HIF-1 signaling pathway and so on in diabetes complications.Conclusion:Ginkgo leaf may reduce inflammation and oxidative stress levels by acting on Akt1,TNF,IL-6,VEGFA,IL-1βand other targets,and inhibit myocardial apoptosis.