| 摘要: |
| 目的基于网络药理学方法以及分子对接探讨桂龙护瘘酊(GT)治疗自体动静脉内瘘(AVF)血管内膜增生(IH)的作用机制。方法:本研究基于HERB数据库并查阅相关文献，筛选GT方中药物的活性成分，按Lipinsk五原则筛选有效成分，并使用PubChem数据库获取成分的Smile，再用Swiss TargetPrediction数据库预测成分靶点。利用GeneCards、Pharmgkb、OMIM数据库收集AVF血管内膜增生相关靶点。利用Venn在线网站得到GT-AVF血管内膜增生的交集靶点Venn图。利用String平台构建以药物、活性成分、潜在靶点的PPI网络，利用DAVID数据库中对其进行GO富集分析和KEGG信号通路分析，采用分子对接进行验证。结果:通过网络药理学研究，GT方中共获取到主要活性成分81个、关键成分预测靶点30个，应用PPI网络得到ACE、NOS3等关键交集靶点。富集分析后得到221个GO相关条目、47条相关KEGG信号通路，GO分析结果主要集中在异种生物分解代谢过程、外源性药物分解代谢过程等，KEGG富集分析关键通路是钙信号通路、神经活性配体-受体相互作用通路等，关键靶点主要富集在ADRB3，NOS3，ADRB1等。分子对接显示(-)-Limonene、(-)-alpha-Pinene、Tridecnoic acid核心成分与NOS3蛋白(PDB: 1d0c)核心靶点具有非常好的结合构象。结论:本研究采用网络药理学与分子对接技术，为GT治疗AVF血管内膜增生提供了(-)-Limonene、(-)-alpha-Pinene及Tridecnoic acid等多靶点；钙信号通路、神经活性配体-受体相互作用通路的作用特点，主要与调控NOS3蛋白表达水平有关，为后期进一步实验、临床研究提供了理论依据，也是对AVF瘘管处局部外用中药复方防治IH进行的新探索。 |
| 关键词: 自体动静脉内瘘 血管内膜增生 桂龙护瘘酊 网络药理学 |
| DOI：10.3969/j.issn.1007-6948.2024.02.023 |
| 投稿时间：2023-09-11 |
| 基金项目:2023年度省卫生健康委科学技术基金项目(gzwkj2023-319)贵州省中医药管理局中医药、民族医药科学技术研究课题(QZYY-2；018-057)；2022年贵州中医药大学研究生教育创新计划项目(YCXZRS202215)；贵州省级中医优势专科建设项目(2024) |
|
| Study on mechanism of Guilong Fistula Protecting Tincture in treating tunica intima hyperplasia of autogenous arteriovenous fistula based on network pharmacology and molecular docking |
| WEN Fu-long，XIE Juan，LI Zheng-sheng |
|
| Abstract: |
| Objective To explore the mechanism of guilong fistula protecting tincture (GT) in treating tunica intima hyperplasia (IH) of autogenous arteriovenous fistula (AVF) based on network pharmacology and molecular docking. Methods This study based on the HERB database and relevant literature review. The active ingredients of the drugs were screened in the GT formula and follow the Lipinsk five principles to screen the active ingredients. PubChem database was used to obtain the Smile of the components, and then Swiss TargetPrediction database was used to predict the target points of the components. Targets related to endovascular hyperplasia of AVF were collected by GeneCards, Pharmgkb and OMIM databases.Venn map of intersection target of GT-AVF tunica intima hyperplasia was obtained by Venn onlinewebsite. a PPI network with drugs, active ingredients, and potential targets was built using the String platform. DAVID database was used for GO enrichment analysis and KEGG signaling pathway analysis. The molecular docking was used for validation. Results Through online pharmacology research, GT obtained a total of 81 main active ingredients and 30 key ingredient prediction targets. PPI network was applied to obtain key intersection targets, such as ACE and NOS3. After enrichment analysis, 221 GO related entries and 47 related KEGG signaling pathways were obtained. The GO analysis results mainly focus on the processes of heterologous biodegradation and exogenous drug metabolism. The key pathways for KEGG enrichment analysis are calcium signaling pathways, neural active ligand receptor interaction pathways, etc. The key targets were mainly enriched in ADRB3, NOS3 and ADRB1 etc. Molecular docking shows that the core components of (-) - Limene, (-) - alpha Pinene and Tridecnoic acid have good binding conformations with the core target of NOS3 protein (PDB: 1d0c). Conclusion This study adopts network pharmacology and molecular docking technology. It provides multiple targets such as (-) - Limonene, (-) - alpha Pinene and Tridecnoic acid for GT to treat AVF tunica intima hyperplasia. The characteristics of the calcium signaling pathway and the neuroactive ligand receptor interaction pathway. Mainly related to regulating the expression level of NOS3 protein. This provides a theoretical basis for further experiments and clinical research in the later stage. It is also a new exploration for the prevention and treatment of IH by using local topical Chinese herbal formulas at the AVF fistula site. |
| Key words: Autologous arteriovenous fistula intimal hyperplasia guilong fistula protecting tinctur network pharmacology |
