Mitigation of ionizing radiation-induced bone marrow suppression by p38 inhibition and G-CSF administration.
Mitigation of ionizing radiation-induced bone marrow suppression by p38 inhibition and G-CSF administration.
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DOI：
10.1269/jrr.11007
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发表时间：
2011
影响因子：
2
通讯作者：
Meng A
中科院分区：
文献类型：
--
作者：
Li D;Wang Y;Wu H;Lu L;Zhang H;Chang J;Zhai Z;Zhang J;Wang Y;Zhou D;Meng A
p38丝裂原活化蛋白激酶（p38）已被证明在暴露于电离辐射（IR）后在造血干细胞和祖细胞中被活化，并且其活化已涉及各种病理条件下的骨髓（BM）抑制。因此，在本研究中，我们调查是否p38活性的抑制单独与SB 203580（SB，特异性p38抑制剂）或与粒细胞集落刺激因子（G-CSF）的组合可以减轻全身照射（TBI）诱导的BM损伤和致死率。我们的研究结果表明，当SB单独使用时，p38抑制对暴露于7.2戈伊TBI的小鼠的30天存活率没有显著影响，但当SB与G-CSF组合时，增加了小鼠的存活率。这种联合效应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，分别与SB或G-CSF处理的小鼠的细胞相比，SB和G-CSF处理的小鼠的BM细胞产生更多的集落形成单位-粒细胞-巨噬细胞（CFUs-GM）和4周鹅卵石区形成细胞（CAFC）。这些发现表明，SB和G-GSF的联合治疗在减轻TBI诱导的急性BM损伤方面比单独使用任一种药物更有效。
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 (CFUs-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.
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DOI：
10.1002/stem.5530080204
发表时间：
1990-03-01
期刊：
INTERNATIONAL JOURNAL OF CELL CLONING
影响因子：
--
作者：
PATCHEN, ML;MACVITTIE, TJ;SOUZA, LM
通讯作者：
SOUZA, LM
影响因子：
20.3
作者：
Navas, Tony A.;Mohindru, Mani;Verma, Amit
通讯作者：
Verma, Amit
影响因子：
3.5
作者：
Park, Eunjin;Ahn, Gin-nae;Jee, Youngheun
通讯作者：
Jee, Youngheun
影响因子：
2
作者：
Liu, Qiang;Jiang, Bo;Jiang, Enhai
通讯作者：
Jiang, Enhai
影响因子：
2.6
作者：
Drouet, Michel;Herodin, Francis
通讯作者：
Herodin, Francis