探索氧化多环芳暴露对炎症性肠病影响的机制
Yufang Hou1, Yuexia Che2, Tiegang Li1
1State Key Laboratory of Digestive Health, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China; State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China.
Ecotoxicology and environmental safety
|October 2, 2025
概括
氧化多环芳 (OPAHs) 通过引起氧化应激和破坏肠道屏障,可以引发炎症性肠病 (IBD). 这项研究确定了关键的基因和相关蛋白质,为OPAH诱导的IBD提供了潜在的治疗点.
科学领域:
- 环境毒理学环境毒理学
- 分子生物学分子生物学
- 胃肠病学 胃肠病学
背景情况:
- 氧化多环芳 (OPAH) 是具有显著毒性的环境污染物.
- 炎症性肠病 (IBD) 是一种由环境因素影响的慢性消化道炎症.
- 将OPAH与IBD发展联系在一起的机制尚不清楚.
研究的目的:
- 调查OPAH和IBD之间的联系.
- 为了确定关键的基因和分子途径涉及到OPAH诱导的IBD.
- 探索OPAH相关的肠道炎症的潜在治疗点.
主要方法:
- 网络毒理学方法用于识别OPAH因子和IBD目标之间的重叠基因.
- 生物信息分析包括STRING,Cytoscape,GO和KEGG通路的丰富.
- 机器学习算法,免疫景观分析,单细胞RNA测序和分子对接.
- 在体外实验中评估OPAH对活性氧物种和肠道屏障功能的影响.
主要成果:
- 确定了15个潜在的目标基因,主要涉及氧化应激,细胞死亡,炎症和免疫反应.
- 突出了AKT1,ALB和APP作为核心枢纽基因,与免疫细胞透密切相关.
- 确认了OPAHs和枢纽蛋白之间的高结合亲缘关系.
- 证明OPAHs增加活性氧物种并损害肠道上皮质屏障功能 in vitro.
结论:
- 阐明了OPAHs对IBD发展的分子机制.
- 提供了与OPAH暴露相关的健康风险的见解.
- 确定了AKT1,ALB和APP作为OPAH诱导IBD的潜在治疗点.
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