通过减轻细胞焦亡来提高放射性暴露后的存活率。
Enhancing survival after ionizing radiation exposure through mitigation of pyroptosis.
机构信息
Center for Free Radical and Antioxidant Health, Department of Environmental and Occupational Health, University of Pittsburgh School of Public Health, 130 Desoto St, Pittsburgh, PA 15261, USA; Safar Center for Resuscitation Research, Department of Critical Care Medicine, University of Pittsburgh Medical Center, 4401 Penn Ave, Pittsburgh, PA 15224, USA; Children's Neuroscience Institute, UPMC Children's Hospital of Pittsburgh, 4401 Penn Ave., Pittsburgh, PA 15224, USA.
Department of Radiation Oncology, University of Pittsburgh Medical Center, 200 Lothrop St, Pittsburgh, PA 15213, USA.
出版信息
Biochim Biophys Acta Mol Basis Dis. 2024 Oct;1870(7):167434. doi: 10.1016/j.bbadis.2024.167434. Epub 2024 Jul 23.
• Pyroptosis, an inflammatory cell death, has been implicated in the pathogenesis of total body irradiation (TBI) so we investigated time course and cell type involvement of key mediators in a murine model. • Pyroptotic mediators were most highly expressed at day 3 post TBI with immune cells from ileum being preferentially activated. • We also investigated the effectiveness of MCC950, a potent pyroptosis inhibitor, in our murine model showing a survival benefit at 50 mg/kg regardless of sex. • Treatment with MCC950 showed elevations in full-length downstream mediator IL-1β in ileum and decreased levels of cleaved IL-1β in splenic tissue.
• 细胞焦亡，一种炎症性细胞死亡，与全身照射（TBI）的发病机制有关，因此我们在小鼠模型中研究了关键介质的时间进程和细胞类型参与。• 在 TBI 后第 3 天，细胞焦亡介质的表达最高，回肠中的免疫细胞优先被激活。• 我们还研究了 MCC950（一种有效的细胞焦亡抑制剂）在我们的小鼠模型中的有效性，结果表明无论性别如何，50mg/kg 的剂量都能提高生存率。• 用 MCC950 治疗后，回肠中全长下游介质 IL-1β升高，而脾组织中 cleaved IL-1β 水平降低。
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