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多糖抑制铁死亡减轻脓毒症心肌损伤:基于NRF2/HO-1通路的药理机制研究

Inhibition of Iron Death by Polysaccharides Ameliorates Myocardial Injury in Sepsis: A Pharmacological Mechanism Study Based on the NRF2/HO-1 Pathway.

作者信息

Niu Zesu, Hu Yi, Yang Long, Meng Xiaorui, Chen Mengfei, Bai Xue, Liu Ruxin, Tang Yujiao, Yang Liting, Xue Weiliang

机构信息

The Third Clinical Medical School Ningxia Medical University Yinchuan China.

Department of Emergency Medicine, People's Hospital of Ningxia Hui Autonomous Region Ningxia Medical University Yinchuan China.

出版信息

Food Sci Nutr. 2025 Sep 17;13(9):e70835. doi: 10.1002/fsn3.70835. eCollection 2025 Sep.

DOI:10.1002/fsn3.70835
PMID:40969909
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12441308/
Abstract

Sepsis remains a leading global cause of mortality, with sepsis-induced myocardial injury (SIMI) being a critical determinant of clinical outcomes. L. (goji berry), a traditional Chinese herb, has demonstrated therapeutic potential in sepsis-related organ injuries through multiple pathways. However, its role and mechanisms in SIMI remain unexplored. A network pharmacology approach identified candidate targets of via TCMSP and SwissTargetPrediction, intersected with sepsis/myocardial injury-related targets from GeneCards. Protein-protein interaction (PPI) networks were constructed using STRING and analyzed via Cytoscape's cytoHubba plugin. Enriched pathways were explored through KEGG/GO analyses. Transcription factor prediction, molecular docking (AutoDock Vina), and molecular dynamics (MD) simulations (GROMACS) were performed for key targets. Experimental validation included in vivo LPS-induced sepsis models and in vitro H9C2 cardiomyocyte assays. This study reveals that alleviates SIMI by modulating the NRF2/HO-1 signaling pathway, positioning it as a novel therapeutic candidate for sepsis-associated cardiac complications.

摘要

脓毒症仍然是全球主要的死亡原因,脓毒症诱导的心肌损伤(SIMI)是临床结局的关键决定因素。枸杞,一种传统的中草药,已通过多种途径在脓毒症相关器官损伤中显示出治疗潜力。然而,其在SIMI中的作用和机制仍未被探索。一种网络药理学方法通过中药系统药理学数据库与分析平台(TCMSP)和瑞士靶点预测工具(SwissTargetPrediction)确定了枸杞的候选靶点,并与来自基因卡片(GeneCards)的脓毒症/心肌损伤相关靶点进行交叉分析。使用STRING构建蛋白质-蛋白质相互作用(PPI)网络,并通过Cytoscape的cytoHubba插件进行分析。通过京都基因与基因组百科全书(KEGG)/基因本体(GO)分析探索富集通路。对关键靶点进行转录因子预测、分子对接(AutoDock Vina)和分子动力学(MD)模拟(GROMACS)。实验验证包括体内脂多糖诱导的脓毒症模型和体外H9C2心肌细胞试验。本研究表明,枸杞通过调节核因子E2相关因子2(NRF2)/血红素加氧酶-1(HO-1)信号通路减轻SIMI,使其成为脓毒症相关心脏并发症的新型治疗候选药物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/94b3/12441308/44fc3e795430/FSN3-13-e70835-g006.jpg
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