2021 年第 2 期 第 16 卷

基于网络药理学探讨肾康注射液治疗慢性肾衰竭的作用机制

Exploration of the active mechanism of Shenkang injection in treating chronic renal failure based on network pharmacology

作者：孙童1孟佳2张帆3秦建国1

英文作者：Sun Tong1 Meng Jia2 Zhang Fan3 Qin Jianguo1

单位：1北京中医药大学东方医院肾病内科100078；2北京中医药大学东方医院重症监护室100078；3大连大学附属中山医院生殖中心116001孙童为北京中医药大学2018级中医内科学专业在读硕士研究生

英文单位：1Department of Nephrology Oriental Hospital of Beijing University of Traditional Chinese Medicine Beijing 100078 China; 2Intensive Care Unit Oriental Hospital of Beijing University of Traditional Chinese Medicine， Beijing 100078 China; 3Reproductive Center Affiliated Zhongshan Hospital of Dalian University Dalian 116001 ChinaSun Tong is Master Degree Candidate Internal Medicine of Traditional Chinese Medicine Speciality Grade 2018 of Beijing University of Traditional Chinese Medicine

关键词：

英文关键词：Chronicrenalfailure;Networkpharmacology;Shenkanginjection;Activemechanism

• 摘要：

• 目的 基于网络药理学探讨肾康注射液治疗慢性肾衰竭（CRF）的可能作用机制。方法 检索中药系统药理学数据库和分析平台筛选肾康注射液所含中药的相应活性成分，并对活性成分进行靶标预测，借助SwissTargetPrediction数据库对预测不到的活性成分靶标进行补充。通过Genecards、drugbank、OMIM等数据库检索CRF疾病的相关靶点。借助Cytoscape软件构建中药-活性成分-靶点网络图以及核心靶点蛋白相互作用网络图。利用Metascape工具对查到的基因进行基因本体论富集分析以及KEGG通路富集分析，探讨潜在靶标可能具有的生物学功能及通路。结果 肾康注射液的主要活性成分包括芦荟大黄素、3′-O-没食子酸、丹参酮ⅡA、黄芩素、豆甾醇、木犀草素、槲皮素、山奈酚等。将筛选获取的肾康注射液的362个靶点及CRF的734个靶点取交集，共获得51个肾康注射液治疗CRF的核心靶点蛋白。肾康注射液治疗CRF的可能核心靶点包括血管内皮生长因子A、肿瘤坏死因子、白细胞介素6、信号传导与转录激活因子3、内皮一氧化氮合成酶3、丝氨酸/苏氨酸蛋白激酶1、表皮生长因子、肿瘤蛋白p53等，其治疗CRF主要通过作用于癌症通路、糖尿病并发症中的糖基化产物-受体信号通路、氮素代谢、胰岛素抵抗、甲状旁腺激素的合成与分泌及作用、药物代谢、腺苷酸活化蛋白激酶信号通路等通路或过程实现。结论 本研究初步表明了肾康注射液治疗CRF具有多成分、多靶点、多通路的特点，为进一步阐释其药理作用机制及新药开发奠定了理论基础。

• Objective To explore the active mechanism of Shenkang injection in treating chronic renal failure(CRF) based on network pharmacology. Methods Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform were used to screen the corresponding active components of Shenkang injection, and to predict targets of active components. Swiss Target Prediction database was used to supplement the unpredictable targets of active components. CRF disease related targets were searched from Genecards, drugbank, OMIM and other databases. Cytoscape software was used to construct the Chinese medicine active ingredient-target network diagram and the core target protein interaction network diagram. The gene ontology enrichment analysis and KEGG pathway enrichment analysis were carried out by using Metascape tools to explore the possible biological functions and pathways of potential targets. Results  The main active components of Shenkang injection were aloe emodin, 3′-O-gallate, dehydrotanshinone ⅡA, baicalein, stigmasterol, luteolin, quercetin, kaempferol and so on. A total of 51 core target proteins of Shenkang injection were obtained by crossing 362 targets of Shenkang injection and 734 targets of CRF. The possible core targets of Shenkang injection for CRF included vascular endothelial growth factor A, tumor necrosis factor, interleukin-6, signal transducer and activator of transcription 3, endothelial nitric oxide synthase 3, serine/threonine protein kinase 1, epidermal growth factor, tumor protein p53, and so on. The pathways or processes of Shenkang injection treating CRF mainly included such as cancer pathway, glycosylation product-receptor signaling pathway in diabetic complications, nitrogen metabolism, insulin resistance, parathyroid hormone synthesis, secretion and action, drug metabolism, and AMP-activated protein kinase signal pathway. Conclusions This study initially shows that Shenkang injection has the characteristics of multi-components, multi-targets and multi-pathways in the treatment of CRF. It is a theoretical foundation for further explanation of Shenkang injection pharmacological mechanism and the development of new drugs.