Department of Radiobiology, Beijing Key Laboratory for Radiobiology, Beijing Institute of Radiation Medicine, Beijing, 100850, China.
Department of Radiotherapy, Nanfang Hospital, Southern Medical University, Guangzhou, 510080, China.
Stem Cell Res Ther. 2022 Sep 6;13(1):461. doi: 10.1186/s13287-022-03162-x.
Hematopoietic stem cell transplantation (HSCT) is the main treatment for acute radiation sickness, especially after fatal radiation. The determination of HSCT for radiation patients is mainly based on radiation dose, hemogram and bone marrow injury severity. This study aims to explore a better biomarker of acute radiation injury from the perspective of systemic immune response.
C57BL/6J female mice were exposed to total body irradiation (TBI) and partial body irradiation (PBI). Changes in haptoglobin (Hp) level in plasma were shown at different doses and time points after the exposure and treatment with amifostine or bone marrow transplantation. Student's t-test/two tailed test were used in two groups. To decide the Hp levels as a predictor of the radiation dose in TBI and PBI, multiple linear regression analysis were performed. The ability of biomarkers to identify two groups of different samples was determined by the receiver operating characteristic (ROC) curve. The results were expressed as mean ± standard deviation (SD). Significance was set at P value < 0.05, and P value < 0.01 was set as highly significant. Survival distribution was determined by log-rank test.
In this study, we found that Hp was elevated dose-dependently in plasma in the early post-irradiation period and decreased on the second day, which can be used as a molecular indicator for early dose assessment. Moreover, we detected the second increase of Hp on the 3rd and 5th days after the lethal irradiation at 10 Gy, which was eliminated by amifostine, a radiation protection drug, while protected mice from death. Most importantly, bone marrow transplantation (BMT) on the 3rd and 5th day after 10 Gy radiation improved the 30-days survival rate, and effectively accelerated the regression of secondary increased Hp level.
Our study suggests that Hp can be used not only as an early molecule marker of radiation injury, but also as an important indicator of bone marrow transplantation therapy for radiation injury, bringing new scientific discoveries in the diagnosis and treatment of acute radiation injury from the perspective of systemic immunity.
造血干细胞移植（HSCT）是治疗急性放射病的主要方法，特别是在致命性放射后。对放射病患者进行 HSCT 的决定主要基于辐射剂量、血象和骨髓损伤程度。本研究旨在从全身免疫反应的角度探索急性放射损伤的更好生物标志物。
C57BL/6J 雌性小鼠接受全身照射（TBI）和半身照射（PBI）。在暴露后不同时间点，观察血浆中结合珠蛋白（Hp）水平的变化，并分别用氨磷汀或骨髓移植进行处理。采用两样本 t 检验/双侧检验进行两组比较。采用多元线性回归分析 Hp 水平是否可作为 TBI 和 PBI 辐射剂量的预测因子。通过受试者工作特征（ROC）曲线确定生物标志物区分两组不同样本的能力。结果表示为均数±标准差（SD）。P 值<0.05 为有统计学意义，P 值<0.01 为高度显著。采用对数秩检验确定生存分布。
本研究发现，Hp 在照射后早期的血浆中呈剂量依赖性升高，并在第二天下降，可作为早期剂量评估的分子指标。此外，我们在 10 Gy 致死照射后第 3 和第 5 天检测到 Hp 的第二次升高，这种升高被放射保护药物氨磷汀消除，同时保护小鼠免于死亡。最重要的是，在 10 Gy 照射后第 3 和第 5 天进行骨髓移植可提高 30 天的存活率，并有效加速二次升高的 Hp 水平的回归。
本研究表明，Hp 不仅可以作为放射损伤的早期分子标志物，还可以作为放射损伤骨髓移植治疗的重要指标，从全身免疫的角度为急性放射损伤的诊断和治疗带来新的科学发现。
