铁致死涉及到由黑纳米颗粒诱导的细胞细胞毒性
Ruolan You1, Yaming Mu1, Jiaqi Zhou1
1School of Public Health, Shandong Second Medical University, Weifang 261053, China.
Toxicology
|April 23, 2024
概括
黑纳米粒子 (BPNPs) 在小鼠中引起生殖毒性,降低胎儿和胎盘体重. 这通过细胞死亡途径铁亡发生,影响热囊细胞功能和活力.
科学领域:
- 生物医学纳米技术 生物医学纳米技术
- 生殖毒理学 生殖毒理学
- 细胞机制 细胞机制
背景情况:
- 黑 (BP) 是一种具有有前途的生物医学应用的新型纳米材料.
- 关于BP的生殖毒性,特别是关于黑纳米粒子 (BPNPs) 的研究有限.
研究的目的:
- 在怀孕小鼠中研究BPNPs的体内生殖毒性.
- 使用体外模型阐明BPNP诱导的生殖毒性背后的分子机制.
- 评估铁质在BPNP诱导的细胞毒性和功能障碍中的作用.
主要方法:
- 使用暴露于BPNPs的孕妇小鼠进行体内研究,评估胎儿和胎盘的参数.
- 在体外实验中使用人体热囊细胞 (HTR8/SVneo) 用BPNPs治疗.
- 细胞活力,增殖,迁移和入侵测定.
- 转录组测序以确定受BPNPs影响的分子通路.
- 生物化学试验用于测量与铁死相关的标记物 (铁,GPX4,FTL,MDA,GSH).
- 用细胞抑制剂和铁灭抑制剂进行治疗.
主要成果:
- 在怀孕的小鼠中,BPNP暴露导致胎儿和胎盘体重减少,胎盘形态改变.
- BPNPs诱导了显著的细胞毒性,减少了增殖,以及损害了 trofhoblast 细胞的迁移和入侵.
- 转录组分析显示,BPNPs诱导铁,由增加的铁,减少的GPX4,增加的FTL和升高的脂质过氧化证实.
- 铁酶抑制剂显著缓解了BPNP诱导的细胞毒性和功能缺陷.
结论:
- 这项研究提供了与BPNPs相关的生殖毒性的第一个证据.
- 通过铁亡,BPNPs诱导热囊细胞功能障碍和死亡.
- 这些发现加深了在生殖环境中对黑纳米材料生物安全性的理解.
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