| 整合用药网络、靶点网络和分子对接技术探究中药治疗气阴两虚兼血瘀型糖尿病肾病的临床用药机制 |
| 投稿时间：2023-10-14 修订日期：2024-04-24 点此下载全文
|
| 引用本文： |
| DOI： |
| 摘要点击次数: 51 |
| 全文下载次数: 0 |
|
|
| 基金项目:中国中医科学院科技创新工程重大攻关项目（CI2021A01206）；时振声“三名”传承工作室（020370002） |
|
| 中文摘要:[摘要] 目的 通过整合用药网络及靶点网络分析中药治疗糖尿病肾病气阴两虚兼血瘀证的组方规律及其具体药理机制，为临床治疗提供科学依据并为新药研发提供参考。 方法 以“糖尿病肾病”“气阴两虚”“血瘀”为主题词，在中国知网、维普资讯、万方医学等数据库的相关文献中提取符合纳排标准的方药并建立方药数据库，运用古今医案云平台进行数据统计并进行用药网络相关分析等，筛选出核心药对及核心处方：通过TCMSP、Genecards、OMIM和TTD数据库筛选出核心处方药物的有效化学成分及其相关靶点、糖尿病肾病(Diabetic Nephropathy, DN)的靶点，并取二者的交集靶点。利用Cytoscape 3.9.1软件及相关插件构建“药物-有效活性成分-交集靶点-疾病”网络及交集靶点PPI网络并进行聚类分析、GO功能富集分析(Gene Ontology)、KEGG通路富集分析(Kyoto encyclopedia of genes and genomes)。 结果 最终纳入229篇文献，筛选出172首方剂，涉及379味中药。在治疗糖尿病肾病气阴两虚兼血瘀证的方药中高频药物中，药多平、寒、微寒、温；药味多辛、甘、苦。常用配伍是黄芪与丹参、茯苓与泽泻、黄芪与当归。用药网络分析得到气阴两虚兼血瘀型糖尿病肾病的核心处方为六味地黄汤合当归补血汤加丹参、金樱子、芡实。核心处方的关键成分为槲皮素、木犀草素、山柰酚、泽泻醇B、芒柄花素等，核心靶点为细胞骨架肌动蛋白(Beta-actin, ACTB)、Janus激酶(Just another kinase 2, JAK2)、细胞间黏附分子-1(Intercellular cell adhesion molecule-1, ICAM-1)、血管细胞黏附分子-1(Vascular cell adhesion molecule 1, VCAM1)、白细胞介素4(Interleukin 4,IL-4)等关键蛋白靶点，可能参与AGEs-RAGE信号通路(Ages-Rage Signaling Pathway)、JAK-STAT信号通路(Jak-Stat Signaling)等。分子对接结果表明网络药理学所预测的核心靶点中的JAK2、ICAM-1、VCAM1、IL4与关键活性成分稳定结合。 结论 中医药治疗气阴两虚兼血瘀型糖尿病肾病的核心处方可通过多个活性成分，作用于多靶点、多通路发挥疗效，可为临床治疗糖尿病肾病药物的应用及研发提供理论基础。 |
| 中文关键词:糖尿病肾病 数据挖据 核心处方 网络药理学 |
| |
| Integrated medication network, target network and molecular docking technology to explore the clinical medication mechanism of traditional Chinese medicine in the treatment of diabetic nephropathy with deficiency of both qi and yin and blood stasis |
|
|
| Abstract:[Abstract] Aim To analyze the prescription rules and specific pharmacological mechanisms of traditional Chinese medicine in the treatment of qi and yin deficiency and blood stasis of Diabetic Nephropathy (DN) by integrating drug network and target network, so as to provide scientific basis for clinical treatment and reference for new drug research and development. Methods Using "diabetic nephropathy""qi and yin deficiency"" blood stasis" as the theme word, we extracted prescriptions and medicines that met the criteria from the relevant literature in the databases of China National Knowledge Infrastructure(CNKI), China Science and Technology Journal Database and Wanfang Medicine, established a prescription-drug database, and used the ancient and modern medical case cloud platform to conduct data statistics and related analyses to screen out core pairs and core prescriptions. The active chemical components and related targets of the core prescriptions and the targets of qi and yin deficiency and blood stasis of DN were screened by TCMSP, Genecards, OMIM and TTD databases, and the intersecting targets were taken. Cytoscape 3.9.1 software and related plug-ins were used to construct the "drug-active ingredient-intersection target-disease" network and intersection target PPI network, and cluster analysis, GO and KEGG analysis were performed. Results Finally, 229 literatures were included, and 172 formulas involving 379 Chinese medicines were selected. Among the high-frequency drugs in the formulas for treating DN with qi and yin deficiency and blood stasis, the drugs were mostly flat, cold, slightly cold, and warm; and the tastes were mostly pungent, sweet, and bitter. The commonly used compatibility is astragalus and salvia miltiorrhiza, poria and alisma, astragalus and angelica. The core prescription for DN with the qi and yin deficiency with blood stasis was obtained from the analysis of the medication network as Liuwei Dihuang Decoction combined with Danggui Buxue Decoction plus Radix Salviae Miltiorrhiza, Rosa laevigata, Euryale ferox. The key components of the core prescription were Quercetin, Kaempferol, Luteolin, Alisol B, and Formononetin, and the core targets were Cytoskeletal actin (ACTB), Janus kinase (JAK2), Intercellular adhesion molecule-1(ICAM-1), Vascular cell adhesion molecule-1 (VCAM1), and Interleukin 4 (IL-4). Key protein targets, which may be involved in AGEs-RAGE Signaling Pathway, JAK-STAT Signaling, and so on. The molecular docking results showed that JAK2, ICAM-1, VCAM1, and IL4 among the core targets predicted by network pharmacology were stably bound to the key active ingredients. Conclusion The core prescription of Chinese medicine for the treatment of qi and yin deficiency with blood stasis type of DN can exert therapeutic effects through multiple active ingredients, acting on multiple targets and pathways, which can provide a theoretical basis for the application and development of drugs for the clinical treatment of DN. |
| keywords:Diabetic nephropathy,Data mining,Core prescription,Network pharmacology |
|
查看全文
查看/发表评论 下载PDF阅读器 |
|
|
|
