China CDC Key Laboratory of Radiological Protection and Nuclear Emergency, National Institute for Radiological Protection, Chinese Center for Disease Control and Prevention, Beijing, 100088, China.
China CDC Key Laboratory of Radiological Protection and Nuclear Emergency, National Institute for Radiological Protection, Chinese Center for Disease Control and Prevention, Beijing, 100088, China.
Biomed Pharmacother. 2019 Jun;114:108806. doi: 10.1016/j.biopha.2019.108806. Epub 2019 Mar 29.
Agents that provide protection against irradiation-induced hematopoietic injury are urgently needed for radiotherapy. We examined the effects of the small molecule, 1,2-propanediol (PPD), on total body irradiation (TBI)-induced hematopoietic injury in C57BL/6 mice. PPD administration 1 h before TBI significantly increased hematopoietic parameters such as white blood cell, platelet, red blood cell, and lymphocyte counts in vivo and enhanced the survival of mice exposed to TBI (7.0 and 7.5 Gy). PPD administration 1 h before TBI improved bone marrow (BM) and spleen recovery after TBI, with increases in both BM cellularity and spleen index. The number of colony-forming-units in bone marrow mononuclear cells (BMNCs) in vitro also increased significantly. PPD pretreatment increased the numbers of hematopoietic stem cells and hematopoietic progenitor cells in BM. Importantly, PPD also maintained endogenous antioxidant status by decreasing levels of malondialdehyde and increasing the expression of reduced glutathione, superoxide dismutase and catalase in the serum of irradiated mice. PPD alleviated the levels of apoptosis in HSCs induced by TBI, thus increasing the proportion of dividing BMNCs. These results suggest that PPD protects against TBI-induced hematopoietic injury through the increased activities of antioxidant enzymes and the inhibition of apoptosis in HSCs. PPD increased the serum levels of granulocyte-colony stimulating factor and interleukin-6 irrespective of TBI. In conclusion, these data suggest that PPD acts as a radioprotector against radiation-induced hematopoietic injury.
目前，临床上急需能预防辐射诱导造血损伤的药物用于放疗。我们研究了小分子 1,2-丙二醇（PPD）对 C57BL/6 小鼠全身照射（TBI）诱导造血损伤的作用。TBI 前 1 小时给予 PPD 可显著增加体内的造血参数，如白细胞、血小板、红细胞和淋巴细胞计数，并提高 TBI 暴露小鼠的存活率（7.0 和 7.5Gy）。TBI 前 1 小时给予 PPD 可改善 TBI 后骨髓（BM）和脾脏的恢复，增加 BM 细胞密度和脾脏指数。体外骨髓单个核细胞（BMNC）集落形成单位的数量也显著增加。PPD 预处理可增加 BM 中造血干细胞和造血祖细胞的数量。重要的是，PPD 还通过降低丙二醛水平和增加血清中还原型谷胱甘肽、超氧化物歧化酶和过氧化氢酶的表达，维持了照射小鼠的内源性抗氧化状态。PPD 减轻了 TBI 诱导的 HSCs 凋亡水平，从而增加了 BMNC 分裂的比例。这些结果表明，PPD 通过增加抗氧化酶的活性和抑制 HSCs 凋亡来保护 TBI 诱导的造血损伤。PPD 增加了粒细胞集落刺激因子和白细胞介素-6 的血清水平，而与 TBI 无关。总之，这些数据表明 PPD 可作为一种辐射防护剂，预防辐射诱导的造血损伤。
