-n-丁甲酸盐对肝转录组的持续作用:能量和脂质代谢途径受损
Eleftheria Theodoropoulou1, Paula Pierozan1, Francesco Marabita2
1Science for Life Laboratory, Department of Environmental Science, Stockholm University, Stockholm, 114 18, Sweden.
Chemosphere
|October 23, 2024
概括
双甲酸 (DBP) 通过破坏蛋白质转化和脂质代谢等关键生物过程,导致小鼠的肝损伤和压力. 这表明DBP可能会导致非酒精性脂肪肝疾病的发展.
科学领域:
- 环境毒理学环境毒理学
- 肝病学 肝病学是一种肝病学.
- 分子生物学分子生物学
背景情况:
- 双甲酸乙 (DBP) 是一种环境污染物,因其肝毒性而闻名.
- 确切的分子机制和DBP诱导的肝损伤的病理后果尚未完全理解.
研究的目的:
- 在成年雄性小鼠中研究DBP暴露的持续性肝转录效应.
- 阐明受肝脏中DBP影响的分子通路和生物过程.
主要方法:
- 成年雄性小鼠口服暴露于DBP (10毫克/公斤/天或100毫克/公斤/天) 五周.
- 用RNA测序分析肝脏基因表达和基因组丰富分析 (GSEA) 来识别受影响的途径.
- 肝脏组织分析以确认分子发现并评估病理变化.
主要成果:
- 暴露于DBP导致了基因表达的剂量依赖性改变,影响了与蛋白质翻译,折叠,亡和脂质代谢相关的途径.
- 在两个DBP治疗组中观察到九个Reactome通路的显著干扰.
- 肝脏组织分析证实了DBP诱导的失调,氧化应激,脂质积累以及TNF-α,ATP和葡萄糖激酶水平的改变.
结论:
- 暴露于DBP会以剂量依赖的方式诱导显著的肝应激和病理损伤.
- DBP破坏关键的细胞功能,包括蛋白质平衡和能量代谢.
- 这些发现表明DBP在非酒精性脂肪肝疾病 (NAFLD) 的病原发生过程中可能发挥作用.
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