NRF2/HO-1通路:在雌激素缺乏下,化物诱导的结肠损伤的潜在调节因素
Meng Gao1, Sai Zhang1, Jing Zhao1
1Henan Key Laboratory of Environmental and Animal Product Safety, Henan University of Science and Technology, Kaiyuan Avenue 263, Luoyang, 471000, Henan, People's Republic of China.
Biological trace element research
|May 3, 2025
概括
过度暴露于化物会损害结肠,尤其是在雌激素缺乏的情况下. 这种损伤涉及Nrf2/HO-1通路,并导致亡的增加.
科学领域:
- 毒理学 毒理学 毒理学
- 胃肠病学 胃肠病学
- 内分泌学 在内分泌学.
背景情况:
- 化物 (F) 过度暴露是肠道微环境破坏的已知危险因素.
- 化物诱导的结肠损伤的精确机制和促成因素,特别是在雌激素缺乏的情况下,需要进一步阐明.
研究的目的:
- 调查核因素红色素2相关因子2 (Nrf2) /血氧酶-1 (HO-1) 途径在化物诱导的结肠损伤中的作用.
- 为了检查卵巢切除术 (OVX) 引起的雌激素缺乏对化物对结肠的影响.
主要方法:
- 建立一个老鼠模型,使用不同水平的化物暴露 (0-100 mg/L) 与OVX.相结合.
- 评估结肠形态,上皮屏障完整性 (occludin,claudin-1),细胞增殖,杯状细胞数和短链脂肪酸 (SCFA) 生产.
- 对Nrf2/HO-1通路,Keap1表达和与亡相关的标记物 (Bcl-2,Bax,caspase-3) 的分析.
主要成果:
- 化物暴露损害了结肠形态,减少了奥克卢丁和克劳丁-1的表达,抑制了上皮细胞的增殖,减少了杯状细胞,减少了SCFA的产生.
- 雌激素缺乏症加剧了化物诱导的结肠屏障损伤和SCFA减少.
- 化物和雌激素缺乏抑制了Nrf2/HO-1通路蛋白,上调的Keap1,下调的Bcl-2,上调的Bax和caspase-3,促进了结肠上皮细胞亡.
结论:
- Nrf2/HO-1通路的障碍与化物诱导的结肠壁损伤有关.
- 雌激素缺乏会显著加剧化物对肠道屏障的毒性,通过亡加剧结肠损伤.
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