Ma Zimeng, Yan Shuo, Zhang Huimin, Du Ruilin, Cheng Xinyue, Bao Siqin, Li Xihe, Song Yongli
Research Center for Animal Genetic Resources of Mongolia Plateau, College of Life Sciences, Inner Mongolia University, Hohhot, China.
The State Key Laboratory of Reproductive Regulation and Breeding of Grassland Livestock, College of Life Sciences, Inner Mongolia University, Hohhot, China.
Front Vet Sci. 2025 Aug 18;12:1617190. doi: 10.3389/fvets.2025.1617190. eCollection 2025.
Cadmium, a major environmental contaminant, induces progressive intestinal damage through bioaccumulation . Elucidating its pathogenic mechanisms is crucial for developing therapeutic interventions.
This study employed multi-omics approaches to systematically investigated cadmium-induced ileal dysfunction in Hu sheep and the intervention mechanisms of sodium octanoate.
Phenotypic assessment revealed cadmium exposure caused intestinal barrier impairment and histopathological changes. Integrated transcriptomic-proteomic analysis revealed cadmium disrupted mitochondrial dysfunction via oxidative phosphorylation pathway inhibition. Leading to reactive oxygen species (ROS) overaccumulation. This ROS surge activated ferroptosis, which exacerbated inflammatory responses through NF-κB signaling. Cross-omics correlation analysis identified ferroptosis-related proteins as key regulators of the NF-κB inflammatory axis, suggesting ferroptosis modulation as a potential therapeutic strategy. Notably, sodium octanoate exhibited potent anti-inflammatory effects through specific binding to ACSL4, a critical ferroptosis regulatory protein, this interaction ameliorated oxidative stress and inflammation cascades while demonstrating therapeutic potential for cadmium-induced inflammation.
Our findings establish the ACSL4/NF-κB axis as a central mechanism in cadmium-induced pathology, highlighting sodium octanoate as a potential therapeutic intervention for pollutant-induced intestinal disorders.
镉是一种主要的环境污染物，通过生物累积诱导肠道进行性损伤。阐明其致病机制对于开发治疗干预措施至关重要。
本研究采用多组学方法系统研究镉诱导的湖羊回肠功能障碍以及辛酸钠的干预机制。
表型评估显示，镉暴露导致肠道屏障受损和组织病理学变化。综合转录组学-蛋白质组学分析表明，镉通过抑制氧化磷酸化途径破坏线粒体功能障碍，导致活性氧（ROS）过度积累。这种ROS激增激活了铁死亡，通过NF-κB信号通路加剧了炎症反应。跨组学相关性分析确定铁死亡相关蛋白是NF-κB炎症轴的关键调节因子，表明调节铁死亡是一种潜在的治疗策略。值得注意的是，辛酸钠通过与关键的铁死亡调节蛋白ACSL4特异性结合表现出强大的抗炎作用，这种相互作用改善了氧化应激和炎症级联反应，同时显示出对镉诱导炎症的治疗潜力。
我们的研究结果确立了ACSL4/NF-κB轴是镉诱导病理过程中的核心机制，突出了辛酸钠作为污染物诱导肠道疾病潜在治疗干预措施的地位。
