Enalapril mitigates focal alveolar lesions, a histological marker of late pulmonary injury by radiation to the lung.
Enalapril mitigates focal alveolar lesions, a histological marker of late pulmonary injury by radiation to the lung.
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DOI：
10.1667/rr3127.1
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发表时间：
2013-04
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;Narayanan J;Joneikis C;Fish BL;Szabo A;Moulder JE;Molthen RC;Jacobs ER;Rao RN;Medhora M
我们研究的目的是确定一种组织学标记物，用于测试减轻肺部晚期辐射损伤的对策。肺纤维化是目前急性放射性肺炎幸存者中描述最充分的“晚期效应”。然而，在对整个胸部进行单剂量辐射后，某些啮齿动物品系在数年内都不会出现强烈的纤维化。我们在受辐射的 WAG/RijCmcr 大鼠的肺部观察到与辐射相关的局灶性肺泡病变，这些病变富含含有胆固醇的巨细胞和巨噬细胞。这些病变首次在肺炎后、胸部接受 13 Gy 辐射剂量后约 21 周观察到，但在未受辐射的大鼠中直到 71 周才观察到。在 64 周的观察中，胆固醇裂缝的数量随着辐射后时间的推移而增加，并且在 13 Gy 后的 30 周，胆固醇裂缝与肺功能恶化的多项指标相关。血管紧张素转换酶 (ACE) 抑制剂依那普利 (25–42 mg/m2/天) 使受辐射肺切片中的胆固醇裂口数量减少，从 18.7 ± 4.2/肺切片减少到 6.8 ± 2.4 (P = 0.029)、5.2 ± 1.9 (P = 0.0051) 和 6.7 ± 1.9 (P = 0.029）分别在照射后1周、5周或15周开始用药并继续用药。此前曾在一种受辐射小鼠的肺部以及接受放射治疗的患者的肺部观察到类似的病变。我们建议，具有胆固醇裂隙的肺泡病变可用作放射性肺损伤严重程度的组织学标志物，并研究其在 WAG/中的缓解情况。
The goal of our study was to identify a histological marker for testing countermeasures for mitigation of late radiation injury to the lung. Pulmonary fibrosis is currently the best described “late effect” in survivors of acute radiation pneumonitis. However, robust fibrosis does not develop in some rodent strains for years after a single dose of radiation to the whole thorax. We observed radiation-associated focal alveolar lesions that were rich in giant cells and macrophages containing cholesterol clefts in the lungs of irradiated WAG/ RijCmcr rats. These lesions were first observed after pneumonitis, around 21 weeks after receiving a radiation dose of 13 Gy to the thorax but not until 71 weeks in unirradiated rats. The number of cholesterol clefts increased with time after irradiation through 64 weeks of observation, and at 30 weeks after 13 Gy, cholesterol clefts were associated with several indices of deterioration in lung function. The number of cholesterol clefts in irradiated lung sections were reduced by the angiotensin converting enzyme (ACE) inhibitor enalapril (25–42 mg/m2/day) from 18.7 ± 4.2/lung section to 6.8 ± 2.4 (P = 0.029), 5.2 ± 1.9 (P = 0.0051) and 6.7 ± 1.9 (P = 0.029) when the drug was started at 1 week, 5 or 15 weeks after irradiation, respectively, and continued. Similar lesions have been previously observed in the lungs of one strain of irradiated mice and in patients following radiotherapy. We propose that alveolar lesions with cholesterol clefts may be used as a histological marker of the severity of radiation lung injury and to study its mitigation in WAG/