| 摘要: |
| ［摘要］ 目的 基于网络药理学和分子对接技术探究纳呋拉啡治疗慢性肾脏病相关性瘙痒（CKD-aP）的作用机制。方法 通过Chemical Book平台、SwissTargetPrediction及GeneCards数据库获取纳呋拉啡的基本信息和作用靶点；使用CTD数据库和GeneCards数据库筛选慢性肾脏病（CKD）与瘙痒相关靶点。相关数据库的数据更新截至2025年7月。构建蛋白质-蛋白质相互作用（PPI）网络。对共同靶点进行基因本体（GO）功能富集分析和京都基因与基因组百科全书（KEGG）通路富集分析。结果 共获得纳呋拉啡作用靶基因100个，CKD相关靶基因4 277个，瘙痒相关靶基因4 091个，纳呋拉啡与CKD-aP共同靶基因49个。PPI网络筛选获得9个关键靶基因。GO富集分析共得到933个富集结果，其中生物过程（BP）主要包括磷酸化、跨膜受体蛋白酪氨酸激酶信号通路、蛋白质磷酸化等；细胞组分（CC）主要包括受体复合物、突触后部、ⅠA类磷脂酰肌醇3-激酶复合体等；分子功能（MF）主要包括蛋白激酶活性、以醇为受体的磷酸转移酶活性、激酶活性等。KEGG富集分析共得到139条通路，主要包括EGFR酪氨酸激酶抑制剂抵抗、PI3K-Akt信号通路、ErbB信号通路等。结论 纳呋拉啡可通过多靶点与多通路治疗CKD-aP，为纳呋拉啡的进一步研究提供了理论依据。 |
| 关键词: 纳呋拉啡 慢性肾脏病相关性瘙痒 网络药理学 |
| DOI：10.3969/j.issn.1674-3806.2025.12.04 |
| 分类号:R 692 |
| 基金项目:国家自然科学基金项目（编号：82204821，82304363）；2024年度慢性病防治与健康教育科研项目（编号：BJMB0012024026014） |
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| Exploration on mechanism of action of nalfurafine in treatment of chronic kidney disease-associated pruritus based on network pharmacology and molecular docking techniques |
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LI Jing, SHI Jingxuan, WANG Xu, ZHANG Zheng, ZHUO Li, LI Wenge
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Department of Nephrology, China-Japan Friendship Hospital, Beijing 100029, China
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| Abstract: |
| ［Abstract］ Objective To explore the mechanism of action of nalfurafine in treatment of chronic kidney disease-associated pruritus(CKD-aP) based on network pharmacology and molecular docking techniques. Methods The basic information and target sites of nalfurafine were obtained via Chemical Book platform, SwissTargetPrediction database and GeneCards database. Comparative Toxicogenomics Database(CTD) and GeneCards database were used to screen the target sites related to chronic kidney disease(CKD) and pruritus. The data update of the relevant databases was up to July 2025. The protein-protein interaction(PPI) network was constructed. Gene Ontology(GO) function enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analysis were performed on the common target sites. Results A total of 100 effect target genes of nalfurafine, 4 277 target genes related to CKD, 4 091 target genes related to pruritus, and 49 nalfurafine and CKD-aP common target genes were obtained. Nine key target genes were obtained through the screening of PPI network. A total of 933 enrichment results were obtained by using GO enrichment analysis, among which biological processes(BP) were mainly involved in phosphorylation, transmembrane receptor protein tyrosine kinase signal pathway and protein phosphorylation, and cellular components(CC) were mainly involved in receptor complex, postsynaptic portion and ⅠA phosphatidylinositol 3-kinase complex, and molecular functions(MF) were mainly involved in protein kinase activity, phosphotransferase activity with ethanol as receptor and kinase activity. A total of 139 pathways were obtained by using KEGG enrichment analysis, which were mainly involved in epidermal growth factor receptor(EGFR) tyrosine kinase inhibitor resistance, PI3K-Akt signal pathway and ErbB signal pathway. Conclusion Nalfurafine can treat CKD-aP via multiple targets and pathways, which provides a theoretical basis for further research on nalfurafine. |
| Key words: Nalfurafine Chronic kidney disease-associated pruritus(CKD-aP) Network pharmacology |
