血小板加速脂质过氧化,并诱导致病性中性粒细胞细胞外陷释放
Madoka Ono1, Masayasu Toyomoto2, Momono Yamauchi1
1Department of Anatomy and Developmental Biology, Graduate School of Medicine, Kyoto University, Kyoto 606-8501, Japan; Department of Drug Discovery Medicine, Graduate School of Medicine, Kyoto University, Kyoto 606-8507, Japan.
血小板通过增加铁和脂质过氧化,促进有害的中性粒细胞外细胞陷 (NET) 的形成. 素是一种脂质过氧化抑制剂,在体外和体内有效抑制了NETosis,提供了潜在的治疗策略.
科学领域:
- 免疫学 免疫学 免疫学
- 细胞生物学 细胞生物学
- 生物化学 生物化学
背景情况:
- 中性细胞外细胞陷 (NETs) 对于宿主防御至关重要,但过度的NETosis会导致诸如败血症等疾病.
- 血小板在NETosis的病理激活中发挥作用.
研究的目的:
- 研究血小板诱导NETosis的机制.
- 为了识别和评估抑制血小板介导的致病性NETosis的化合物.
主要方法:
- 同时刺激中性粒细胞与脂多糖和血小板在体外.
- 对脂质过氧化抑制剂的查.
- 在体外和体内评估素对NETosis和脂质过氧化的作用.
主要成果:
- 血小板诱导中性粒细胞的铁积累和脂质过氧化,促进NETosis.
- 素 (8-甲基-N-基拉尼尔-6-nonamide) 抑制了脂质过氧化,并在体外抑制了NETosis.
- 在小鼠肺炎模型中,素减弱的脂多糖诱导的NETosis.
结论:
- 血小板诱导的NETosis是由铁积累和脂质过氧化介导的.
- 用素向脂质过氧化为NETosis相关疾病提供了一种新的治疗方法.
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