基于代谢组学和蛋白组学研究砷暴露对肥胖孕鼠肝脏代谢分子网络的影响  

Impact of arsenic exposure on the hepatic metabolic molecular network in obese pregnant mice using metabolomics and proteomics

作　　者：蔡丽静 王妍[2] 谭峻峰 周海霞 梁诗佳 吴衍 张洁 CAI Lijing;WANG Yan;TAN Junfeng;ZHOU Haixia;LIANG Shijia;WU Yan;ZHANG Jie(School of Public Health,Xiamen University,Xiamen 361102,China;School of Public Health,Fujian Medical University,Fuzhou 350122,China)

机构地区：[1]厦门大学公共卫生学院,福建厦门361102 [2]福建医科大学公共卫生学院,福建福州350122

出　　处：《色谱》2025年第1期50-59,共10页Chinese Journal of Chromatography

基　　金：国家自然科学基金项目(22076157,22306027);福建省自然科学基金项目(2022J01710,2020J01236)。

摘　　要：砷是普遍存在的环境毒物,可能影响生物体的正常生理过程。尽管已有研究探讨了砷对健康的影响,但砷暴露对肥胖孕妇肝脏代谢的影响及其作用机制尚不明确。本研究旨在通过高脂饮食诱导肥胖孕鼠模型,并采用灌胃方式模拟孕期砷暴露,以探究其对肝脏代谢的影响。孕鼠砷暴露后,我们利用代谢组学和蛋白组学技术,结合病理生化分析,对肝脏组织进行了深入研究。结果显示,砷暴露显著增加了肥胖孕鼠肝脏中的脂质累积,并伴随着炎症因子和氧化应激标志物的升高。代谢组学分析揭示了砷暴露对脂质代谢通路,特别是花生四烯酸代谢的显著影响。此外,蛋白组学分析确认了与脂质合成、氧化应激和炎症反应相关的蛋白质表达水平发生了变化。这些结果表明,砷暴露可能通过多种代谢途径和蛋白质调节通路,对肥胖孕鼠肝脏的脂质代谢产生显著影响。本研究不仅为理解砷暴露与肥胖及相关代谢性疾病之间的关系提供了新的科学视角,也为环境健康风险评估和公共卫生政策的制定提供了重要参考。Arsenic is a ubiquitous environmental toxin that can affect normal physiological processes.Although the health impacts of arsenic have been investigated,its influence on hepatic metabolism in obese pregnant women and the underlying mechanisms remain unclear.Multi-omics analysis,including metabolomics and proteomics,can improve the understanding of arsenic-induced hepatotoxicity in obese pregnant women.This study aimed to investigate the adverse effects of gestational arsenic exposure on hepatic metabolism in high-fat-diet-induced obese pregnant mice.Following arsenic exposure during pregnancy,the liver tissue was evaluated comprehensively using metabolomics and proteomics techniques combined with pathological and biochemical analyses.Arsenic exposure not only significantly increased lipid accumulation in the livers of obese pregnant mice but also elevated inflammatory factors and oxidative stress markers.Specifically,histopathological examination revealed more steatosis,inflammatory cell infiltration,and hepatocyte ballooning in the livers of arsenic-exposed mice than in those of controls.These changes indicate that arsenic exposure exacerbates hepatic lipid accumulation and induces liver damage in the context of obesity.Metabolomic analysis provided further insight into the metabolic-level disruption caused by arsenic exposure.Significant changes were observed in lipid metabolism pathways,particularly the arachidonic acid metabolism pathway.As arachidonic acid and its metabolites play important roles in inflammation and oxidative stress,this pathway may be critical in arsenic-induced hepatotoxicity.Additionally,proteomic analysis showed differences in the expression levels of several key proteins involved in lipid synthesis,oxidative stress,and inflammatory response.Notably,oxidative-stress-related proteins,including glutathione peroxidase 4(GPX4),were upregulated,suggesting an increased oxidative burden.In summary,there are complex interaction mechanisms among arsenic exposure,inflammatory response,and related

关 键 词：砷 肥胖 孕鼠 肝脏 代谢组学 蛋白组学 

分 类 号：O658[理学—分析化学]