双乙醇B作为双A的替代品诱导的跨代肝毒性
Huifeng Yue1, Yangcheng Hu2, Xiaoyun Wu2
1Shanxi Key Laboratory of Coal-based Emerging Pollutant Identification and Risk Control, Research Center of Environment and Health, College of Environment and Resource, Shanxi University, Taiyuan, Shanxi 030006, China; Shandong Key Laboratory of Environmental Processes and Health, School of Environmental Science and Engineering, Shandong University, Qingdao, Shandong 266237, China.
双乙烯 (BPB) 暴露会导致后代的肝损伤,影响胆固醇,昼夜节律和氧化应激. 特定的基因 (Tmem87b,Fkbp1a,Ppard,Slc23a2) 被确定为早期检测和治疗反应的生物标志物.
科学领域:
- 环境毒理学环境毒理学
- 内分泌学 在内分泌学.
- 肝病学 肝病学是一种肝病学.
背景情况:
- 双A (BPA) 是一种内分泌干扰物,引起肝脏毒性.
- 越来越多地使用像Bisphenol B (BPB) 这样的结构模拟物.
- 后代的肝脏发育在怀孕期间容易受到内分泌干扰者的影响.
研究的目的:
- 调查BPB诱导的肝毒性和后代的跨代效应.
- 确定与BPB相关的肝功能障碍相关的基因标记物和信号通路.
- 探索BPB毒性的调节机制.
主要方法:
- 动物模型直接或母体暴露于BPB (300μg/kg bw/day).
- 评估生化指标和组织病理变化.
- 生物信息学分析以将BPB暴露与肝损伤相关联,并验证人类肝细胞癌 (HCC) 中的基因标记物.
主要成果:
- 直接暴露于BPB导致亚临床肝毒性,降低胆固醇,扰乱昼夜节律,并通过Tmem87b/Fkbp1a诱导化学抵抗.
- 通过Ppard-Slc23a2失调,母亲的BPB暴露导致后代的肝扩大,高胺酶,氧化应激和脂质失衡.
- 在人类HCC中,Tmem87b,Fkbp1a,Ppard和Slc23a2具有预后意义.
结论:
- 高血压通过昼夜干扰和氧化应激路径诱导肝毒性.
- 已识别的基因 (Tmem87b/Fkbp1a/Ppard/Slc23a2) 作为早期检测和预测治疗反应的双重生物标志物.
- BPB对后代的肝脏健康构成风险,具有潜在的跨代影响.
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