基于网络药理学和实验验证探讨五苓散防治顺铂肾毒性的作用机制  

Mechanism of Wuling San in Preventing and Treating Cisplatin-induced Nephrotoxicity Based on Network Pharmacology and Animal Experiments

作　　者：李刘生 蔡琳琳[2] 吴煜[2] LI Liu-sheng;CAI Lin-lin;WU Yu(Department of Oncology,Beijing Hospital of Integrated Traditional Chinese and Western Medicine,Beijing 100039;Department of Oncology,Xiyuan Hospital,China Academy of Chinese Medical Sciences,Beijing 100091)

机构地区：[1]北京中西医结合医院肿瘤科,北京100039 [2]中国中医科学院西苑医院肿瘤科,北京100091

出　　处：《世界中西医结合杂志》2023年第8期1587-1595,共9页World Journal of Integrated Traditional and Western Medicine

基　　金：国家重点研发计划中医药现代化研究(2017YFC1700606);中国中医科学院科技创新工程项目(C2021A01803)。

摘　　要：目的 基于网络药理学和实验验证研究五苓散防治顺铂肾毒性的作用机制。方法 在中草药系统药理学平台(TCMSP)筛选药物活性成分及靶点;使用OMIM、Genecards数据库筛选疾病靶点;使用Cytoscape 3.7.2软件构建“药物-成分-靶点-疾病”关系网络图;使用STRING数据库构建蛋白互作(PPI)网络,基于拓扑分析筛选核心靶点;基因本体论(GO)富集分析和京都基因与基因组(KEGG)通路分析。建立顺铂肾毒性小鼠模型,分别采用低剂量(13 g/kg)、高剂量(26 g/kg)五苓散处理,检测血清肌酐(Creatinine,CRE)、尿素氮(Blood urea nitrogen,BUN)水平,对肾组织进行HE染色,采用TUNEL法检测细胞凋亡,采用qPCR检测肿瘤坏死因子-α(Tumor necrosis factor-α,TNF-α)、白细胞介素-1β(Interleukin-1β,IL-1β)mRNA的表达水平。结果 网络药理学部分获得关键靶点有TNF、IL-1β等,生物过程主要涉及炎症反应、凋亡的调控等,主要信号通路有TNF信号通路、IL-17信号通路等。动物实验证实,五苓散能够降低BUN、CRE,改善肾脏病理损伤,减轻肾组织细胞凋亡和降低肾脏炎症指标TNF-α、IL-1β mRNA。结论 五苓散可能通过减轻肾组织炎症反应和降低肾组织细胞凋亡水平改善顺铂肾毒性。Objective To explore the mechanism of Wuling San in preventing and treating cisplatin-induced nephrotoxicity based on network pharmacology and experimental verification.Methods Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP)was used to screen active components and targets.Disease-related targets were obtained from the OMIM and Genecards databases.The “drug-component-target-disease” network was constructed using Cytoscape 3.7.2 software.The protein-protein interaction(PPI)network was plotted using the STRING database,and core targets were selected through topological analysis.Gene Ontology(GO)enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analysis were performed.A cisplatin-induced nephrotoxicity model was established in mice,and Wuling San was administered at low(13 g/kg)and high(26 g/kg)doses.Serum creatinine(CRE)and blood urea nitrogen(BUN)levels were measured.Kidney tissues were subjected to HE staining.Cell apoptosis was assessed using the TUNEL method.The expression levels of tumor necrosis factor-α(TNF-α)and interleukin-1β(IL-1β)mRNA were measured using qPCR.Results Network pharmacology identified key targets including TNF and IL-1β.Biological processes involved inflammatory response and apoptosis regulation,while main signaling pathways included the TNF signaling pathway and IL-17 signaling pathway.Animal experiments confirmed that Wuling San could reduce BUN and CRE levels,improve renal histopathological damage,alleviate kidney tissue cell apoptosis,and lower renal inflammatory markers TNF-α and IL-1β mRNA.Conclusion Wuling San may ameliorate cisplatin-induced nephrotoxicity by alleviating renal tissue inflammation and reducing levels of renal tissue cell apoptosis.

关 键 词：网络药理学 动物实验验证 五苓散 顺铂肾毒性 机制 炎症 凋亡 

分 类 号：R285.6[医药卫生—中药学]