针对葡萄糖皮质体受体的抗体减轻了AFB1诱导的小鼠肝毒性
Mindie Zhao1, Yulan Zhao1, Jie Liu1
1Key Laboratory of Animal Physiology & Biochemistry, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, PR China; National Key Laboratory of Meat Quality Control and Cultured Meat Development, Nanjing 210095, PR China.
Ecotoxicology and environmental safety
|February 25, 2025
概括
阿弗拉托xin B1 (AFB1) 通过降低葡萄糖皮质体受体 (GR) 和增加特定的microRNAs,导致肝损伤. 用抗体向这些microRNAs减少了小鼠的AFB1毒性.
科学领域:
- 毒理学 毒理学 毒理学
- 分子生物学分子生物学
- 肝病学 肝病学是一种肝病学.
背景情况:
- 甲素B1 (AFB1) 是一种肝毒素,具有复杂的相互作用,涉及皮质和葡萄糖皮质受体 (GR).
- 微RNAs (miRNAs) 参与调节AFB1毒性,但它们在GR介导途径中的作用尚不清楚.
- 研究GR向的miRNA为AFB1诱导的肝损伤提供了潜在的治疗途径.
研究的目的:
- 调查GR和相关miRNAs在AFB1诱导的肝毒性中的作用.
- 评估GR向抗体在减轻AFB1毒性的有效性,体内和体外.
- 为了确定新型的治疗目标,阿弗拉托克辛诱导的肝脏疾病.
主要方法:
- 小鼠被暴露在AFB1中以诱导肝毒性,随后对肝脏组织进行GR表达和miRNA配置文件的分析.
- 用AFB1治疗AML12肝细胞以评估细胞毒性,GR水平和miRNA表达.
- 针对GR的抗体 (antagomir141/200a/495-3p) 用于抑制特定的miRNAs在体外和体内.
主要成果:
- 在小鼠中,AFB1暴露导致肝炎,氧化应激,减少排毒,降低GR蛋白.
- 观察到miR141-3p,miR200a-3p,miR384-5p,miR183-5p,miR181a-5p和miR181b-5p的上调,确定它们是GR调节剂.
- 抑制miR141/200a/495-3p降低了AML12细胞中的AFB1诱导的细胞毒性,而对抗体减轻了小鼠的肝毒性.
结论:
- AFB1诱导的肝毒性涉及GR的下调和特定的GR向miRNAs的上调.
- 用抗体药物向miR141/200a/495-3p显示了缓解AFB1肝损伤的治疗潜力.
- 这项研究提供了关于管理偏素暴露和相关肝脏疾病的新策略的见解.
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