Timing of captopril administration determines radiation protection or radiation sensitization in a murine model of total body irradiation.
Timing of captopril administration determines radiation protection or radiation sensitization in a murine model of total body irradiation.
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卡托普利的给药时间决定了全身辐射小鼠模型中的辐射防护或辐射敏化。
DOI：
10.1016/j.exphem.2010.01.004
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发表时间：
2010-04
影响因子：
2.6
通讯作者：
Day, Regina M.
中科院分区：
文献类型：
--
作者：
Davis, Thomas A.;Landauer, Michael R.;Mog, Steven R.;Barshishat-Kupper, Michal;Zins, Stephen R.;Amare, Mihret F.;Day, Regina M.
血管紧张素 II (Ang II) 是一种有效的血管收缩剂，影响造血细胞的生长和发育。关于 ACE 抑制剂对辐射引起的造血系统损伤的影响，已有不同的研究结果。我们研究了 ACE 抑制剂卡托普利的不同治疗方案对辐射引起的造血损伤的影响。 C57BL/6 小鼠要么接受假辐射，要么接受 60Co 全身辐射（0.6 Gy/min）。在水中提供卡托普利相对于照射的不同时间段。在未经治疗的小鼠中，7.5 Gy 照射后 30 天的存活率为 50%。照射前 7 天的卡托普利治疗可产生 100% 致死率的放射增敏作用，并且成熟血细胞迅速下降。相比之下，在辐射后 1 小时开始并持续 30 天的卡托普利治疗导致 100% 存活，成熟血细胞和多谱系造血祖细胞的恢复得到改善。在未受辐射的对照小鼠中，卡托普利双相调节 Lin− 骨髓祖细胞循环。 2天后，卡托普利抑制G0-G1转变，更多细胞进入静止状态。然而，卡托普利治疗 7 天后，与未治疗的对照小鼠相比，Linprogenitor 细胞循环增加。这些发现表明，ACE 抑制通过调节造血祖细胞周期来影响辐射后的造血恢复。卡托普利治疗相对于辐射暴露的时间对幸存的造血干细胞的生存能力和再生能力有不同的影响，因此可能导致辐射防护或辐射致敏。
Angiotensin II (Ang II), a potent vasoconstrictor, affects the growth and development of hematopoietic cells. Mixed findings have been reported for the effects of ACE inhibitors on radiation-induced injury to the hematopoietic system. We investigated the consequences of different regimens of the ACE inhibitor captopril on radiation-induced hematopoietic injury. C57BL/6 mice were either sham irradiated or were exposed to 60Co total body irradiation (0.6 Gy/min). Captopril was provided in the water for different time periods relative to irradiation. In untreated mice, the survival rate from 7.5 Gy was 50% at 30 days postirradiation. Captopril treatment for 7 days prior to irradiation resulted in radiosensitization with 100% lethality and a rapid decline of mature blood cells. In contrast, captopril treatment beginning 1 hour postirradiation and continuing for 30 days resulted in 100% survival, with improved recovery of mature blood cells and multilineage hematopoietic progenitors. In nonirradiated control mice captopril biphasically modulated Lin− marrow progenitor cell cycling. After 2 days, captopril suppressed G0-G1 transition and a greater number of cells entered a quiescent state. However, after 7 days of captopril treatment Linprogenitor cell cycling increased compared to untreated control mice. These findings suggest that ACE inhibition affects hematopoietic recovery following radiation by modulating the hematopoietic progenitor cell cycle. The timing of captopril treatment relative to radiation exposure differentially affects the viability and repopulation capacity of spared hematopoietic stem cells and therefore can result in either radiation protection or radiation sensitization.
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影响因子：
5.9
作者：
CASATO, M;PUCILLO, LP;BONOMO, L
通讯作者：
BONOMO, L
影响因子：
6.5
作者：
Chisi, JE;Briscoe, CV;Wdzieczak-Bakala, J
通讯作者：
Wdzieczak-Bakala, J
影响因子：
3.4
作者：
MOULDER, JE;COHEN, EP;HILL, P
通讯作者：
HILL, P
影响因子：
20.3
作者：
Charrier, S;Michaud, A;Vainchenker, W
通讯作者：
Vainchenker, W
影响因子：
2
作者：
Day, Regina M.;Barshishat-Kupper, Michal;Landauer, Michael R.
通讯作者：
Landauer, Michael R.