Department of Regenerative Medicine, Naval Medical Research Center, Silver Spring, MD, USA.
Exp Hematol. 2010 Apr;38(4):270-81. doi: 10.1016/j.exphem.2010.01.004. Epub 2010 Jan 29.
Angiotensin II (Ang II), a potent vasoconstrictor, affects the growth and development of hematopoietic cells. Mixed findings have been reported for the effects of angiotensin-converting enzyme (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 exposed to (60)Co 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 in 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 G(0)-G(1) transition and a greater number of cells entered a quiescent state. However, after 7 days of captopril treatment Lin(-) progenitor 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.
血管紧张素 II（Ang II）是一种强效的血管收缩剂，会影响造血细胞的生长和发育。血管紧张素转换酶（ACE）抑制剂对造血系统辐射损伤的影响存在混合结果。我们研究了不同 ACE 抑制剂卡托普利方案对辐射诱导的造血损伤的后果。
C57BL/6 小鼠接受假照射或（60）Co 全身照射（0.6 Gy/min）。卡托普利在照射前不同时间加入水中。
未治疗的小鼠，7.5 Gy 照射后 30 天的存活率为 50%。照射前 7 天给予卡托普利治疗可导致辐射敏化，死亡率为 100%，成熟血细胞迅速减少。相比之下，照射后 1 小时开始并持续 30 天的卡托普利治疗可使 100%的小鼠存活，成熟血细胞和多谱系造血祖细胞恢复良好。在未照射的对照小鼠中，卡托普利使 Lin(-)骨髓祖细胞周期呈双相调节。2 天后，卡托普利抑制 G0-G1 转换，更多的细胞进入静止状态。然而，与未治疗的对照组相比，7 天后卡托普利治疗的 Lin(-)祖细胞周期增加。
这些发现表明，ACE 抑制通过调节造血祖细胞周期影响辐射后造血的恢复。卡托普利治疗相对于辐射暴露的时间不同，会对未受照射的造血干细胞的存活和再殖能力产生不同的影响，从而导致辐射保护或辐射敏化。
