Accelerated hematopoietic recovery with angiotensin-(1-7) after total body radiation.
Accelerated hematopoietic recovery with angiotensin-(1-7) after total body radiation.
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DOI：
10.3109/09553002.2012.676228
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发表时间：
2012-06
影响因子：
2.6
通讯作者：
Dizerega GS
中科院分区：
文献类型：
--
作者：
Rodgers KE;Espinoza T;Roda N;Meeks CJ;Hill C;Louie SG;Dizerega GS
血管紧张素（1-7）[A（1-7）]是肾素血管紧张素系统（RAS）的一种成分，可刺激骨髓抑制后的造血恢复。在一项I/IIa期临床试验中，化疗后血小板减少减少A（1-7）。在这项研究中，A（1-7）的能力，以提高恢复后全身照射（TBI）显示与辐射诱导的造血损伤的特别关注。将小鼠暴露于铯137 γ射线的TBI（剂量为2-7戈瑞[戈伊]），随后用A（1-7）处理，典型剂量为100-1000 μg/kg，一次或每天一次，持续指定的天数，这取决于研究。动物经颈背皮下注射0.1ml药物的盐水溶液。测定血液和骨髓细胞的回收率。还评估了TBI和A（1-7）对存活率和出血时间的影响。放射暴露后每日给予A（1-7）可改善生存率（从60%至92-97%），并减少TBI后第30天的出血时间。此外，A（1-7）增加骨髓中早期混合祖细胞（3- 5倍）、巨核细胞（2- 3倍）、髓系（3- 6倍）和红系（2- 5倍）祖细胞，并减少辐射诱导的血小板减少症（RIT）（高达2倍）。将治疗次数减少至每周3次也改善了骨髓恢复并降低了RIT。由于核事故或/和恐怖袭击情况下的应急响应者和医疗保健系统可能不堪重负，因此确定了延迟开始治疗的后果。A（1-7）治疗可延迟5天，但仍能有效降低RIT或加速骨髓恢复。本文提供的数据表明，A（1-7）可减少临界辐射照射的后果，并可在初始照射后很好地开始治疗，当在照射后2天和照射后5天开始治疗时，对早期反应的造血祖细胞的影响最大，对晚期反应的祖细胞和减少血小板减少症。即使在辐射暴露后几天给予A（1-7）也有一定的效果。
Angiotensin (1–7) [A(1–7)] is a component of the renin angiotensin system (RAS) that stimulates hematopoietic recovery after myelosuppression. In a Phase I/IIa clinical trial, thrombocytopenia after chemotherapy was reduced by A(1–7). In this study, the ability of A(1–7) to improve recovery after total body irradiation (TBI) is shown with specific attention to radiation-induced hematopoietic injury. Mice were exposed to TBI (doses of 2–7 Gray [Gy]) of cesium 137 gamma rays, followed by treatment with A(1–7), typical doses were 100–1000 μg/kg given once or once daily for a specified number of days depending on the study. Animals are injected subcutaneously via the nape of the neck with 0.1 ml drug in saline. The recovery of blood and bone marrow cells was determined. Effects of TBI and A(1–7) on survival and bleeding time was also evaluated. Daily administration of A(1–7) after radiation exposure improved survival (from 60% to 92–97%) and reduced bleeding time at day 30 after TBI. Further, A(1–7) increased early mixed progenitors (3- to 5-fold), megakaryocyte (2- to 3-fold), myeloid (3- to 6-fold) and erythroid (2- to 5-fold) progenitors in the bone marrow and reduced radiation-induced thrombocytopenia (RIT) (up to 2-fold). Reduction in the number of treatments to 3 per week also improved bone marrow recovery and reduced RIT. As emergency responder and healthcare systems in case of nuclear accident or/and terrorist attack may be overwhelmed, the consequence of delayed initiation of treatment was ascertained. Treatment with A(1–7) can be delayed up to 5 days and still be effective in the reduction of RIT or acceleration of bone marrow recovery. The data presented in this paper indicate that A(1–7) reduces the consequences of critical radiation exposure and can be initiated well after initial exposure with maximal effects on early responding hematopoietic progenitors when treatment is initiated 2 days after exposure and 5 days after exposure for the later responding progenitors and reduced thrombocytopenia. There was some effect of A(1–7) even when given days after radiation exposure.
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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。
影响因子：
2.6
作者：
Davis, Thomas A.;Landauer, Michael R.;Mog, Steven R.;Barshishat-Kupper, Michal;Zins, Stephen R.;Amare, Mihret F.;Day, Regina M.
通讯作者：
Day, Regina M.
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：
15.9
作者：
Mrug, M;Stopka, T;Prchal, JT
通讯作者：
Prchal, JT
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.