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本研究通过体外实验与网络药理学相结合的方法分析芍药苷治疗糖尿病视网膜病变的相关作用机制。制备高糖环境下视网膜血管内皮细胞的体外模型，探究芍药苷对糖尿病视网膜病变的保护作用；从TCMSP、 UniProt、 PubChem、 PharmMapper、 SwisstargetPrediction、 GeneCards、 OMIM、 DrugBank、 TTD数据库获取芍药苷和糖尿病视网膜病变的作用靶点，使用韦恩图获取核心靶点；基于STRING数据库，采用Cytoscape构建蛋白质-蛋白质相互作用网络和“药物-靶点-疾病”网络；应用DAVID数据库对核心靶点进行GO功能富集分析和KEGG通路富集分析，并用AutoDock软件将芍药苷与核心靶点进行分子对接验证。体外实验结果显示，芍药苷能显著抑制视网膜血管内皮细胞的增殖，降低其迁移能力并减少管腔形成长度。网络药理学结果显示共获取芍药苷治疗糖尿病视网膜病变的核心靶点154个，其中度值较高的靶点包括VEGFA、 IL6等。GO功能共富集到705个GO条目，主要涉及细胞对药物的反应、血管内皮细胞迁移的调节、细胞增殖的调节等生物过程；KEGG通路富集分析共富集到137条通路，主要包括AGE-RAGE信号通路和PI3K-Akt信号通路。分子对接结果显示，芍药苷分子与核心靶点VEGFA、 IL6的结合能力良好。本研究表明芍药苷可能通过多靶点、多通路调节视网膜血管内皮细胞的增殖、迁移能力及管腔形成长度等发挥治疗糖尿病视网膜病变的作用。
Abstract：In this study, the combination of in vitro experiments and network pharmacology was used to explore the mechanism of paeoniflorin in treating diabetic retinopathy. An in vitro model of retinal vascular endothelial cells under high glucose environment was prepared to explore the protective effect of paeoniflorin on diabetic retinopathy. The targets of paeoniflorin and diabetic retinopathy were obtained from TCMSP, UniProt, PubChem, PharmMapper, SwisstargetPrediction, GeneCards, OMIM, DrugBank, TTD databases, and the core targets were obtained by Venn diagram. Based on the STRING database, the protein-protein interaction network and a “drug-target-disease” network were constructed using Cytoscape; The DAVID database was used to carry out GO biological process and KEGG pathway enrichment to analyze the core target, and the AutoDock software was used to carry out molecular docking verification between paeoniflorin and the core target. In vitro experimental results show that paeoniflorin can significantly inhibit the proliferation and migration ability of retinal vascular endothelial cells and reduce the length of lumen formation. The results of network pharmacology show that a total of 154 core targets for the treatment of diabetic retinopathy with paeoniflorin have been obtained, among which higher degree targets include VEGFA, IL6, etc. The GO function is enriched to 705 GO items, mainly involving cell response to drugs, the regulation of vascular endothelial cell migration, regulation of cell proliferation and other biological processes; The KEGG pathway enrichment analysis enriched a total of 137 pathways, mainly including the AGE-RAGE signaling pathway and the PI3K-Akt signaling pathway. Molecular docking results showed that paeoniflorin molecules had good binding ability to core targets VEGFA and IL6. This study suggests that paeoniflorin may play a role in the treatment of diabetic retinopathy by regulating the proliferation, migration ability and lumen formation length of retinal vascular endothelial cells through multiple targets and pathways.
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基本信息:
DOI：10.13417/j.gab.043.000522
中图分类号:R285
引用信息:
[1]李景景,凌芸,唐慧新,等.基于网络药理学探究芍药苷治疗糖尿病视网膜病变的机制[J].基因组学与应用生物学,2024,43(03):522-533.DOI:10.13417/j.gab.043.000522.
基金信息:
国家自然科学基金面上项目(81874384); 浦东新区卫建委联合攻关项目(PW2021D-03)共同资助
2023-10-17
2023-10-17
2023-10-17