Department of Physiology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA.
Division of Pulmonary, Allergy, and Critical Care, Department of Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA.
Int J Mol Sci. 2019 Jan 5;20(1):176. doi: 10.3390/ijms20010176.
Updated measurements of charged particle fluxes during the transit from Earth to Mars as well as on site measurements by Curiosity of Martian surface radiation fluxes identified potential health hazards associated with radiation exposure for human space missions. Designing mitigation strategies of radiation risks to astronauts is critical. We investigated radiation-induced endothelial cell damage and its mitigation by LGM2605, a radioprotector with antioxidant and free radical scavenging properties. We used an in vitro model of lung vascular networks (flow-adapted endothelial cells; FAECs), exposed to gamma rays, low/higher linear energy transfer (LET) protons (3⁻4 or 8⁻10 keV/µm, respectively), and mixed field radiation sources (gamma and protons), given at mission-relevant doses (0.25 gray (Gy)⁻1 Gy). We evaluated endothelial inflammatory phenotype, NLRP3 inflammasome activation, and oxidative cell injury. LGM2605 (100 µM) was added 30 min post radiation exposure and gene expression changes evaluated 24 h later. Radiation induced a robust increase in mRNA levels of antioxidant enzymes post 0.25 Gy and 0.5 Gy gamma radiation, which was significantly decreased by LGM2605. Intercellular cell adhesion molecule-1 (ICAM-1) and NOD-like receptor protein 3 (NLRP3) induction by individual or mixed-field exposures were also significantly blunted by LGM2605. We conclude that LGM2605 is a likely candidate to reduce tissue damage from space-relevant radiation exposure.
更新的地球到火星过渡期间带电粒子通量的测量以及好奇号在火星表面辐射通量的现场测量，确定了与人类太空任务辐射暴露相关的潜在健康危害。设计宇航员辐射风险的缓解策略至关重要。我们研究了辐射诱导的内皮细胞损伤及其通过 LGM2605 的缓解作用，LGM2605 具有抗氧化和自由基清除特性的辐射防护剂。我们使用肺血管网络（适应流动的内皮细胞；FAECs）的体外模型，暴露于伽马射线、低/更高线性能量转移（LET）质子（分别为 3⁻4 或 8⁻10 keV/µm）和混合场辐射源（伽马和质子），给予与任务相关的剂量（0.25 格雷（Gy）⁻1 Gy）。我们评估了内皮炎症表型、NLRP3 炎性小体激活和氧化细胞损伤。LGM2605（100 µM）在辐射暴露后 30 分钟添加，并在 24 小时后评估基因表达变化。辐射诱导 0.25 Gy 和 0.5 Gy 伽马射线后抗氧化酶的 mRNA 水平显著增加，LGM2605 显著降低了这种增加。单独或混合场暴露诱导的细胞间黏附分子-1（ICAM-1）和 NOD 样受体蛋白 3（NLRP3）的诱导也明显被 LGM2605 减弱。我们得出结论，LGM2605 是一种可能的候选药物，可以减少与太空相关的辐射暴露造成的组织损伤。
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