草甘膦农药通过改变小鼠肝脏代谢谱引起肝毒性  

Glyphosate pesticide induces hepatotoxicity in mice by altering liver metabolic profiles

作　　者：齐磊[1,2] 程宇 钞虹[1] 杨晓蕾[1] 朱金峰[1] 李洪杰 李刚 QI Lei;CHENG Yu;CHAO Hong;YANG Xiao-lei;ZHU Jin-feng;LI Hong-jie;LI Gang(School of Public Health,Qiqihar Medical University,Qiqihar,Heilongjiang 161006,China;不详)

机构地区：[1]齐齐哈尔医学院公共卫生学院,黑龙江齐齐哈尔161006 [2]齐齐哈尔医学科学院,黑龙江齐齐哈尔161006

出　　处：《现代预防医学》2025年第5期905-910,共6页Modern Preventive Medicine

基　　金：齐齐哈尔市科技计划联合引导项目(LSFGG-2024100);国家自然科学基金项目(82103869);齐齐哈尔医学科学院科研项目(QMSI2019M-23,QMSI2023B-13,2024-ZDPY-003,QMSI2019M-05)。

摘　　要：目的 基于代谢组学方法研究草甘膦的肝脏毒效应及毒作用机制。方法 40只昆明雄性小鼠随机分为对照组、低剂量组[50 mg/(kg·d)]、中剂量组[250 mg/(kg·d)]和高剂量组[500 mg/(kg·d)],草甘膦农药经口途径染毒30 d。检测小鼠肝脏脏器系数、病理改变、肝功参数等指标。应用UPLC-MS检测小鼠肝代谢谱,选择多元统计分析方法筛选差异代谢物,基于KEGG平台开展差异代谢物富集分析。结果 与对照组相比较,中剂量和/或高剂量草甘膦染毒小鼠肝细胞呈现不同程度水肿和炎症改变,血清ALT、TBLI、DBILI和GLU水平显著升高。草甘膦降低了肝脏黄嘌呤、次黄嘌呤、嘧啶等核苷酸代谢产物含量,胆碱、卵磷脂和鞘氨醇等细胞膜成分,硫胺素和视黄醛等维生素含量及马尿酸和4-氨基丁醛等氨基酸代谢物含量;提升了葡萄糖-6-磷酸、果糖-1-磷酸、核糖-1-磷酸等糖代谢产物含量。此外,肝功指标ALT、TBLI、DBILI水平与上述代谢物存在相关性。结论 草甘膦染毒可以通过影响小鼠肝脏核苷酸代谢、糖代谢、氨基酸代谢、磷脂代谢和维生素代谢等途径损伤肝脏细胞结构与功能。Objective To investigate the hepatotoxic effects and mechanisms of glyphosate using metabolomics approaches.Methods Forty male Kunming mice were randomly divided into control,low-dose(50 mg/kg·d),medium-dose(250 mg/kg·d),and high-dose(500 mg/kg·d)groups,with glyphosate administered orally for 30 days.The liver organ coefficients,pathological changes,and liver function parameters were measured.UPLC-MS was employed to analyze the liver metabolic profiles,and multivariate statistical methods were utilized to identify differential metabolites,followed by enrichment analysis based on the KEGG platform.Results Compared to the control group,mice exposed to medium and/or high doses of glyphosate exhibited varying degrees of edema and inflammation in liver cells,along with significantly elevated serum levels of ALT,TBILI,DBILI,and GLU.Glyphosate exposure reduced the levels of nucleotide metabolites such as hypoxanthine,xanthine,and pyrimidine,as well as cellular membrane components like choline,phosphatidylcholine,and sphingosine.It also decreased the levels of vitamins such as thiamine and retinal,and amino acid metabolites including Hom vanillic acid and 4-aminobutyraldehyde.Conversely,it increased the levels of carbohydrate metabolites such as glucose-6-phosphate,fructose-1-phosphate,and ribose-1-phosphate.Furthermore,liver function indicators ALT,TBILI,and DBILI were correlated with the aforementioned metabolites.Conclusion Glyphosate exposure can damage the structure and function of liver cells in mice by affecting nucleotide metabolism,carbohydrate metabolism,amino acid metabolism,phospholipid metabolism,and vitamin metabolism.

关 键 词：草甘膦农药 肝脏 代谢组学 毒效应 

分 类 号：R114[医药卫生—卫生毒理学] R575.5[医药卫生—公共卫生与预防医学]