Enalapril mitigates radiation-induced pneumonitis and pulmonary fibrosis if started 35 days after whole-thorax irradiation.
Enalapril mitigates radiation-induced pneumonitis and pulmonary fibrosis if started 35 days after whole-thorax irradiation.
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DOI：
10.1667/rr13350.1
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发表时间：
2013-11
影响因子：
3.4
通讯作者：
Medhora M
中科院分区：
文献类型：
--
作者：
Gao F;Fish BL;Moulder JE;Jacobs ER;Medhora M
放射性攻击或核事故的受害者可能会受到胸部高剂量、异质性辐射照射，导致肺损伤。我们的目标是制定对策，以减轻这种伤害。我们使用WAG/RijCmcr大鼠，在210天内接受13戈伊的全胸腔照射以诱导肺纤维化。血管紧张素转换酶（ACE）抑制剂依那普利作为这些损伤的缓解剂进行了评估，在两个剂量（18和36毫克/平方米/天）和8个时间表：开始于7，35，70，105和140天，并继续到210天或开始于7天，并停止在30，60或90天后，全胸照射。最早开始日期为辐照后7天，这将为分诊和剂量测定提供足够的时间窗。在我们的机构动物护理和使用委员会（IACUC）允许的情况下，35天后的存活率也被记录为肺炎的主要终点。使用Sircol生物化学测定法测量肺胶原蛋白来评估肺纤维化。我们的研究结果表明，短期的依那普利剂量从7-90天改善生存。然而，肺纤维化仅通过较高剂量的依那普利（36 mg/m2/天）减轻。该药物的最晚有效开始日期为照射后35天。这些结果表明，ACE抑制剂可以在照射后至少一个月开始用于减轻肺炎和/或肺纤维化。
Victims of a radiological attack or nuclear accident may receive high-dose, heterogeneous exposures from radiation to the chest that lead to lung damage. Our goal is to develop countermeasures to mitigate such injuries. We used WAG/RijCmcr rats receiving 13 Gy to the whole thorax to induce pulmonary fibrosis within 210 days. The angiotensin converting enzyme (ACE) inhibitor enalapril was evaluated as a mitigator of these injuries at two doses (18 and 36 mg/m2/day) and 8 schedules: starting at 7, 35, 70, 105 and 140 days and continuing to 210 days or starting at 7 days and stopping at 30, 60 or 90 days after whole-thorax irradiation. The earliest start date at 7 days after irradiation would provide an adequate window of time for triage and dosimetry. Survival after 35 days, as permitted by our Institutional Animal Care and Use Committee (IACUC) was also recorded as a primary end point of pneumonitis. Pulmonary fibrosis was evaluated using the Sircol biochemical assay to measure lung collagen. Our results indicated that a short course of either dose of enalapril from 7–90 days improved survival. However, pulmonary fibrosis was only mitigated by the higher dose of enalapril (36 mg/m2/day). The latest effective start date for the drug was 35 days after irradiation. These results indicate that ACE inhibitors can be started at least a month after irradiation for mitigation of pneumonitis and/or pulmonary fibrosis.