付少杰, 张丽, 王雪瑶, 许钟镐. 以葡萄糖转运蛋白1为潜在作用靶点的传统中药治疗糖尿病肾病的机制探究[J]. 临床肾脏病杂志, 2022, 22(10): 819-826. DOI: 10.3969/j.issn.1671-2390.2022.10.005
    引用本文: 付少杰, 张丽, 王雪瑶, 许钟镐. 以葡萄糖转运蛋白1为潜在作用靶点的传统中药治疗糖尿病肾病的机制探究[J]. 临床肾脏病杂志, 2022, 22(10): 819-826. DOI: 10.3969/j.issn.1671-2390.2022.10.005
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    Fu Shao-jie, Zhang Li, Wang Xue-yao, Xu Zhong-gao. Mechanism of traditional Chinese medicine with GLUT1 as a potential therapeutic target for diabetic nephropathy[J]. Journal of Clinical Nephrology, 2022, 22(10): 819-826. DOI: 10.3969/j.issn.1671-2390.2022.10.005
    Citation: Fu Shao-jie, Zhang Li, Wang Xue-yao, Xu Zhong-gao. Mechanism of traditional Chinese medicine with GLUT1 as a potential therapeutic target for diabetic nephropathy[J]. Journal of Clinical Nephrology, 2022, 22(10): 819-826. DOI: 10.3969/j.issn.1671-2390.2022.10.005
    shu

    以葡萄糖转运蛋白1为潜在作用靶点的传统中药治疗糖尿病肾病的机制探究

    Mechanism of traditional Chinese medicine with GLUT1 as a potential therapeutic target for diabetic nephropathy

      摘要
    • 摘要: 目的 探究传统中药中以葡萄糖转运蛋白1（glucose transporters type 1，GLUT1）为潜在作用靶点的活性成分及其治疗糖尿病肾病（diabetic nephropathy，DN）的可能机制。方法 通过中药系统药理数据库与分析平台筛选出以GLUT1为潜在作用靶点的活性成分，含有这些成分的中药以及这些成分的全部作用靶点；通过Genecards、OMIM、Drugban以及PharmGKB数据库获取DN相关靶点；利用Cytoscape软件构建“中药-成分-靶点”网络；通过STRING数据库和Cytoscape软件制作蛋白相互作用网络，并进行拓扑学分析寻找核心靶点；使用分子对接软件（AutoDock Vina）对GLUT1和作用于它的活性成分进行分子对接，验证它们的结合能力；利用R 4.1.1软件中的ClusterProfiler包对靶点基因进行GO和KEGG富集分析。结果 研究发现异甘草素和大黄素是中药中以GLUT1为潜在作用靶点的活性成分，它们的作用靶点共计53个，DN相关靶点3371个，交集靶点40个，其中核心靶点16个。GLUT1是异甘草素和大黄素治疗DN的核心靶点之一，且分子对接结果显示GLUT1与异甘草素和大黄素均具有稳定的结合能力。GO富集结果显示对非生物性刺激的反应、对氧气水平的反应等生物过程与异甘草素和大黄素对DN的治疗作用相关； KEGG富集分析结果显示白细胞介素17、肿瘤坏死因子、晚期糖基化终产物及其受体以及丝裂原活化蛋白激酶等信号通路与异甘草素和大黄素对DN的治疗作用相关。结论 异甘草素和大黄素是中药中以GLUT1为潜在作用靶点的活性成分，它们通过多靶点、多通路对DN产生治疗作用。GLUT1是它们治疗DN的核心靶点之一，它们可直接和间接调节GLUT1从而对DN的治疗起到重要作用。

       

      Abstract: Objective To explore the active ingredients of traditional Chinese medicine（TCM） with GLUT1 as a potential target and elucidate its possible therapeutic mechanism for diabetic nephropathy（DN）. Methods Active ingredients with GLUT1 as a potential target，herbal medicines containing these ingredients and the targets of all these ingredients were screened by TCM Systems Pharmacology Database & Analysis Platform（TCMSP）. Target genes of DN were retrieved from the databases of GeneCards，OMIM，Drugbank and PharmGKB. The network of “herbs-compounds-targets” was constructed by Cytoscape software；PPI network was constructed through STRING database and Cytoscape software and topological parameters were performed for identifying core targets；molecular docking for GLUT1 acting upon active ingredients was performed for verifying binding capability. Analyses of Gene Ontology（GO）and Kyoto Encyclopedia of Gene and Genomes（KEGG）pathway enrichment were performed by Bioconductor R software. Results Isoliquiritigenin and emodin were two active TCM ingredients with GLUT1 as a potential target and there were a total of 53 acting targets. And 3371 DN-related and 40 intersection targets were identified and 16 were core targets. GLUT1 was one of core therapeutic targets for DN by isoliquiritigenin and emodin. Molecular docking results indicated that GLUT1 had stable binding to both of them. GO enrichment analysis showed that such biological processes as cellular response to abiotic stimulus and response to oxygen level were associated with the therapeutic effects of isoliquiritigenin and emodin on DN. KEGG enrichment analysis revealed that IL-17，TNF，AGERAGE and MAPK signaling pathway were associated with the therapeutic effects of isoliquiritigenin and emodin on DN. Conclusion Isoliquiritigenin and emodin are two active TCM ingredients with GLUT1 as a potential target. The therapeutic effects on DN are mediated through multiple targets and pathways. GLUT1 is one of core therapeutic targets of DN. Through direct and indirect actions，GLUT1 play important regulatory roles in the treatment of DN.

       

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