Institute of Radiation Medicine, Chinese Academy of Medical Science and Peking Union Medical Collage, Tianjin Key Laboratory of Molecular Nuclear Medicine, Tianjin, China.
J Radiat Res. 2011;52(6):712-6. doi: 10.1269/jrr.11007. Epub 2011 Oct 5.
p38 mitogen-activated protein kinases (p38) has been shown to be activated in hematopoietic stem and progenitors cells after exposure to ionizing radiation (IR) and its activation has been implicated in bone marrow (BM) suppression under various pathological conditions. Therefore, in the present study we investigated whether inhibition of p38 activity alone with SB203580 (SB, a specific p38 inhibitor) or in combination with granulocyte colony-stimulating factor (G-CSF) can mitigate total body irradiation (TBI)-induced BM damage and lethality. Our results showed that p38 inhibition with SB had no significant effect on the 30-day survival rates of the mice exposed to 7.2 Gy TBI when it was used alone but increased the survival of the mice when it was combined with G-CSF. This combined effect may be attributable to a better preservation or stimulation of hematopoietic stem and progenitor cells, because BM cells from SB and G-CSF-treated mice produced more colony forming units-granulocyte-macrophage (CFU-GM) and 4-week cobblestone area forming cells (CAFCs) than the cells from either SB or G-CSF-treated mice after TBI in a colony forming cell assay and a CAFC assay, respectively. These findings suggest that the combined therapy with SB and G-GSF is more effective in mitigating TBI-induced acute BM injury than either agent alone.
p38 丝裂原活化蛋白激酶（p38）在暴露于电离辐射（IR）后已被证明在造血干细胞和祖细胞中被激活，其激活已被牵连到各种病理条件下骨髓（BM）抑制。因此，在本研究中，我们研究了单独用 SB203580（SB，一种特异性 p38 抑制剂）或与粒细胞集落刺激因子（G-CSF）联合抑制 p38 活性是否可以减轻全身照射（TBI）引起的 BM 损伤和致死性。我们的结果表明，当单独使用 SB 抑制 p38 时，对暴露于 7.2 Gy TBI 的小鼠的 30 天存活率没有显著影响，但与 G-CSF 联合使用时增加了小鼠的存活率。这种联合作用可能归因于更好地保存或刺激造血干细胞和祖细胞，因为在集落形成细胞测定和 CAFC 测定中，来自 SB 和 G-CSF 处理的小鼠的 BM 细胞在 TBI 后产生更多的集落形成单位-粒细胞-巨噬细胞（CFU-GM）和 4 周鹅卵石区域形成细胞（CAFCs），而不是来自 SB 或 G-CSF 处理的小鼠的细胞。这些发现表明，SB 和 G-GSF 的联合治疗比单独使用任何一种药物更能有效减轻 TBI 引起的急性 BM 损伤。
