儿童脓毒性休克早期诊断标志物的转录组学筛选与热毒清颗粒网络药理学研究
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R285

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河南省科技攻关项目(252102310502);河南省高等学校重点科研项目(25A360003)


Transcriptomic Screening of Early Diagnostic Biomarkers for Pediatric Septic Shock and Network Pharmacology of Redu Qing Granules
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    摘要:

    目的:本研究旨在通过转录组学分析鉴定儿童脓毒性休克(PSS) 的早期诊断标志物,并分析中 药复方热毒清颗粒抗PSS的活性成分及作用机制。方法:通过比较PSS患儿与正常对照样本的转录组数据筛选 差异表达基因(DEGs),并进行京都基因与基因组百科全书(KEGG)、基因本体(GO) 富集分析以及基因集 变异分析(GSVA)。结合GeneCards数据库的脓毒性休克相关基因(SSRGs),采用LASSO回归和随机森林算法 筛选关键标志物,并通过受试者工作特征(ROC) 曲线评估诊断效能。利用网络药理学和分子对接技术分析热 毒清颗粒的活性成分及其潜在靶点。结果:共鉴定到672个DEGs,主要富集于补体与凝血级联反应、中性粒 细胞胞外诱捕网形成、Th17细胞分化、抗原加工与呈递等免疫炎症通路。筛选出Toll样受体5(TLR5)、谷胱 甘肽还原酶(GSR)、杀菌通透性增加蛋白(BPI)、白细胞介素2 受体亚基β (IL2RB)、S100 钙结合蛋白 A9(S100A9) 等5个PSS早期标志物,联合指标的ROC曲线下面积(AUC) 达0.99。热毒清颗粒的5种主要活 性成分(色胺酮、羽扇豆醇、维生素D3、β-胡萝卜素、乌苏酸) 可能通过调控7 个核心靶点结合珠蛋 白(HP)、中性粒细胞弹性蛋白酶(ELANE)、穿孔素1(PRF1)、脂质运载蛋白2(LCN2)、S100A9、热休克 蛋白β1(HSPβ1)、肝细胞生长因子(HGF) 发挥抗PSS作用。分子对接显示维生素D3和β-胡萝卜素与LCN2 的结合最稳定。结论:TLR5、GSR、BPI、IL2RB、S100A9等5个基因可作为PSS的早期诊断标志物,热毒清 颗粒可能通过多成分-多靶点调控免疫炎症反应发挥治疗PSS的作用。

    Abstract:

    Abstract: Objective: To identify early diagnostic biomarkers for pediatric septic shock (PSS) through transcriptomic analysis and to investigate the active components and mechanisms of action of the traditional Chinese medicine compound Redu Qing Granules against PSS. Methods:Differentially expressed genes (DEGs) were screened by comparing the transcriptomic data of PSS children with normal controls, and Kyoto Encyclopedia of Genes and Genomes (KEGG), Gene Ontology (GO) enrichment analyses, and gene set variation analysis (GSVA) were performed. Combined with septic shock-related genes (SSRGs) from the GeneCards database, key biomarkers were screened using LASSO regression and random forest algorithms, and diagnostic efficacy was evaluated using the receiver operating characteristic (ROC) curve. Network pharmacology and molecular docking techniques were used to analyze the active components and potential targets of Redu Qing Granules. Results: A total of 672 DEGs were identified, mainly enriched in immune-inflammatory pathways such as complement and coagulation cascades, neutrophil extracellular trap formation,Th17 cell differentiation,and antigen processing and presentation. Five early PSS biomarkers (TLR5, GSR, BPI, IL2RB, and S100A9) were screened, with a combined ROC area under the curve (AUC) of 0.99. The five main active components of Redu Qing Granules (tryptanthrin, lupeol, vitamin D3, β-carotene,and ursolic acid) may exert anti-PSS effects by regulating seven core target proteins (HP,ELANE, PRF1,LCN2,S100A9,HSPB1,and HGF). Molecular docking showed that vitamin D3 and β-carotene had the most stable binding with LCN2. Conclusion:The five genes TLR5,GSR,BPI,IL2RB,and S100A9 can serve as early diagnostic biomarkers for PSS,and Redu Qing Granules may exert therapeutic effects on PSS through multi-component and multi-target regulation of immune-inflammatory responses.

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刘怡闻,张华丽,张嵩亭,王文宝,朱吾元,袁磊.儿童脓毒性休克早期诊断标志物的转录组学筛选与热毒清颗粒网络药理学研究[J].新中医,2025,57(23):236-242

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