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聚乙烯纳米塑料通过PDGFRα依赖的肝星细胞激活加剧迪布甲酸诱导的肝纤维化
Eun Bok Baek1, Jae-Hong Ko2, Aya Yamamura3
1Department of Physiology, College of Medicine, Jeju National University, Jeju 63243, Republic of Korea.
Environmental pollution (Barking, Essex : 1987)
|February 4, 2026
概括
环境污染物,如纳米塑料和迪布甲酸,通过激活PDGFRα通路,导致肝损伤. 针对这种途径可能为环境诱导的肝病提供治疗策略.
科学领域:
- 环境健康 环境健康
- 毒理学 毒理学 毒理学
- 肝病学 肝病学是一种肝病学.
背景情况:
- 纳米塑料颗粒 (NPs) 和双甲 (DBP) 是广泛存在的环境污染物.
- 血小板衍生生长因子受体α (PDGFRα) 在塑料诱导的肝损伤和DBP介导纤维化中的作用尚未完全理解.
研究的目的:
- 调查PDGFRα在DBP诱导的肝毒性和纤维化中的机制性作用.
- 探索共暴露纳米塑料和DBP对肝损伤的协同效应.
- 评估PDGFRα作为环境诱导肝病的潜在治疗点.
主要方法:
- HSC-肝细胞共同培养 (LX-2-HepG2或LO2) 和转录基因分析 (RNA-seq).
- 在体内研究涉及PDGFRα抗体中和药理抑制与伊马替尼.
- 评估细胞活力,细胞因子水平,细胞亡,增殖和纤维素标志物.
- 通过初级HSC对纳米塑料颗粒 (PS-NP) 内化的研究.
主要成果:
- 暴露于DBP降低了肝细胞活力,增加了促炎细胞因子,并诱导了亡.
- DBP刺激了HSC的增殖和调高了纤维素标记物,通过对线信号增强了肝损伤.
- RNA-seq揭示了肝细胞中不同的途径激活 (LO2中的apoptotic/TNF,LX-2中的oncogenic/PI3K-Akt).
- 抑制PDGFRα显著减弱了DBP诱导的肝纤维化和炎症.
- 聚乙烯纳米塑料 (PS-NP) 被PDGFRα阳性HSC内部化,增加PDGFRα和PI3K的表达.
- 同时暴露于PS-NP和DBP导致了协同性肝毒性和恶化的纤维性损伤.
结论:
- PDGFRα是DBP诱导的肝纤维化和炎症的关键媒介.
- 同时暴露于纳米塑料和DBP对肝脏有复杂的毒性影响.
- PDGFRα代表了由环境污染物引起的肝脏疾病的潜在治疗标.
- 共同暴露范式对于评估复杂的环境污染物混合物的健康风险至关重要.
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