基于非靶向代谢组学分析黄曲霉毒素B1对小鼠肝脏代谢及相关通路的影响

doi:10.3969/j.issn.1004-616x.2026.01.008

摘要/Abstract

摘要： 目的：基于非靶向代谢组学探讨黄曲霉毒素B1(AFB1)染毒对小鼠肝脏的影响，为研究AFB1的肝毒性及肝损伤机制提供数据支持。方法：将BALB/c小鼠随机分为两组，适应性培养7 d后，AFB1组每天灌胃给予0.75 mg/kg的AFB1，对照组给予等体积生理盐水，30 d后处死小鼠，取肝组织液氮速冻保存，然后用LC-MS对小鼠肝组织进行代谢组学检测，鉴定两组间的差异代谢物，并对其参与的代谢通路进行富集分析。结果： AFB1作用30 d后BALB/c小鼠肝脏代谢物表达水平发生了明显改变，共检测到1 608种代谢物，其中32种是AFB1组独有代谢物；与对照组相比，检测到201种表达差异代谢物，其中107种显著上调，94种显著下调。AFB1作用后代谢谱的变化可以归属到12条代谢通路，其中11条通路与代谢相关，1条与基因信息加工相关；上调的代谢物富集到5条代谢通路，下调的代谢物富集到7条通路。此外本研究发现GSSG/GSH比值、氧代十二烷二酸、18-羟基二十碳五烯酸等可作为AFB1诱导肝损伤的生物标志物。结论： AFB1染毒显著改变了小鼠肝脏的代谢谱，并且这种改变可归属到代谢通路和信息加工通路，侧面证实了AFB1导致肝损伤的传统机制，同时也为深入理解长期低剂量AFB1暴露对小鼠肝毒性可能的机制提供了代谢组学层面的数据支持。

关键词: 非靶向代谢组学, 黄曲霉毒素B1, BALB/c小鼠, 肝脏代谢, 代谢通路

Abstract: OBJECTIVE： To investigate effects of aflatoxin B1 (AFB1) exposure on livers of mice from a metabolic perspective， thereby providing data support for elucidating mechanisms of AFB1-induced hepatotoxicity. METHODS： BALB/c mice were randomly divided into two groups. After a 7-day acclimatization period，the AFB1 group received 0.75 mg/kg AFB1 daily via oral gavage，while the control group was administered an equivalent volume of physiological saline. These mice were sacrificed after 30 days， and liver tissues were rapidly frozen and stored in liquid nitrogen. Metabolomic analysis of liver tissues was performed using liquid chromatography-mass spectrometry (LC-MS). Differential metabolites between the two groups were identified，and enrichment analysis of the involved metabolic pathways was conducted. RESULTS： After 30 days of AFB1 exposure，metabolite expression profiles in livers of mice were significantly altered. A total of 1 608 metabolites were detected，among which 32 were unique to the AFB1 group. Compared with the control group，201 differential metabolites were identified，of which 107 were significantly upregulated and 94 were significantly downregulated. Changes in metabolic profiles were associated with the regulation of 12 metabolic pathways： 11 related to metabolism and 1 related to genetic information processing. The upregulated metabolites were enriched in five pathways. The downregulated metabolites were enriched in seven pathways. Additionally， this study identified the GSSG/GSH ratio， oxododecanedioic acid， and 18-hydroxy eicosapentaenoic acid as potential biomarkers of AFB1-induced liver injury. CONCLUSION： AFB1 exposure significantly altered metabolic profiles of livers，with alterations attributed to pathways including metabolism and information processing. These findings corroborate traditional mechanisms of AFB1-induced liver injury and provide metabolomic-level data for understanding potential mechanisms underlying long-term，low-dose AFB1 exposure-induced hepatotoxicity in mice.

Key words: non-targeted metabolomics, aflatoxin B1, BALB/c mice, liver metabolism, metabolic pathways

中图分类号:

R992

罗绣, 孙震晓. 基于非靶向代谢组学分析黄曲霉毒素B1对小鼠肝脏代谢及相关通路的影响[J]. 癌变·畸变·突变, 2026, 38(1): 48-53,74.

LUO Xiu, SUN Zhenxiao. Aflatoxin B1 on liver metabolic disturbances in mice based on non-targeted metabolomics[J]. Carcinogenesis, Teratogenesis & Mutagenesis, 2026, 38(1): 48-53,74.

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