Combined Hydration and Antibiotics with Lisinopril to Mitigate Acute and Delayed High-dose Radiation Injuries to Multiple Organs
Combined Hydration and Antibiotics with Lisinopril to Mitigate Acute and Delayed High-dose Radiation Injuries to Multiple Organs
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DOI：
10.1097/hp.0000000000000554
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发表时间：
2016-11-01
期刊：
影响因子：
2.2
通讯作者：
Medhora, Meetha
中科院分区：
文献类型：
--
作者：
Fish, Brian L.;Gao, Feng;Medhora, Meetha
NIAID辐射和核对策计划正在开发医疗制剂，以减轻放射性核攻击或事故可能产生的辐射的急性和延迟影响。迄今为止，大多数此类医疗对策都是针对单一器官损伤而开发的。血管紧张素转换酶（ACE）抑制剂已被用于减轻大鼠辐射引起的肺、皮肤、脑和肾损伤。据报道，ACE抑制剂也可减少放射肿瘤患者的正常组织并发症。在目前的研究中，作者已经开发了一种大鼠部分体照射（腿部外照射）模型，该模型具有最小限度的骨髓保留（一条腿屏蔽），可导致多个器官的急性和晚期损伤。在该模型中，ACE抑制剂赖诺普利（类似于24 mg m(-2) d）在照射后7天开始在饮用水中口服，并持续到150天)减轻了12.5 gy腿部PBI后肺和肾脏的晚期效应。同样在这个模型中，在剂量高达13 Gy后，短期的生理盐水水化和抗生素治疗减轻了急性辐射综合征。将这种支持治疗与赖诺普利方案相结合，可减轻13 gy腿部PBI后长达150天的总发病率。此外，赖诺普利在生长因子g - csf (100 g kg（-1) d（-1）从第1-14天）存在时是一种有效的缓解剂，fda批准用于放射性核事件。总之，通过将赖诺普利（fda批准用于其他适应症）与水合和抗生素联合使用，减轻了多器官的急性和延迟性辐射损伤。
The NIAID Radiation and Nuclear Countermeasures Program is developing medical agents to mitigate the acute and delayed effects of radiation that may occur from a radionuclear attack or accident. To date, most such medical countermeasures have been developed for single organ injuries. Angiotensin converting enzyme (ACE) inhibitors have been used to mitigate radiation-induced lung, skin, brain, and renal injuries in rats. ACE inhibitors have also been reported to decrease normal tissue complication in radiation oncology patients. In the current study, the authors have developed a rat partial-body irradiation (leg-out PBI) model with minimal bone marrow sparing (one leg shielded) that results in acute and late injuries to multiple organs. In this model, the ACE inhibitor lisinopril (at similar to 24 mg m(-2) d(-1) started orally in the drinking water at 7 d after irradiation and continued to 150 d) mitigated late effects in the lungs and kidneys after 12.5-Gy leg-out PBI. Also in this model, a short course of saline hydration and antibiotics mitigated acute radiation syndrome following doses as high as 13 Gy. Combining this supportive care with the lisinopril regimen mitigated overall morbidity for up to 150 d after 13-Gy leg-out PBI. Furthermore, lisinopril was an effective mitigator in the presence of the growth factor G-CSF (100 g kg(-1) d(-1) from days 1-14), which is FDA-approved for use in a radionuclear event. In summary, by combining lisinopril (FDA-approved for other indications) with hydration and antibiotics, acute and delayed radiation injuries in multiple organs were mitigated.