Ward W F, Solliday N H, Molteni A, Port C D
Radiat Res. 1983 Nov;96(2):294-300.
To determine the role of endothelial dysfunction in the pathogenesis of radiation-induced pulmonary injury, lung angiotensin-converting enzyme (ACE) activity, arterial perfusion, and ultrastructure were examined from 1 to 150 days after a single exposure of 25 Gy of 60Co gamma rays to the right hemithorax of rats. Arterial perfusion to the irradiated right lung increased during the first 2 weeks, then decreased to approximately 80% of the left lung value at 30 days postirradiation. Perfusion of the irradiated lung continued to decline, and by 90-150 days was only 40% of that of the shielded lung. ACE activity in the irradiated right lung did not change significantly until 30 days after exposure, when it decreased to 72% of that in the left lung. ACE activity in the right lung declined steadily from 30 to 90 days postirradiation, then reached a plateau through 150 days at less than 20% of normal. Perivascular and interstitial edema was evident at 1 day after irradiation and persisted for 30 days. Endothelial cells exhibited blebbing, fragmentation, and increased basement membrane at 30 days. Mast cells were present in the septa, but interstitial collagen was not increased at that time. From 90 to 150 days postexposure, progressive obliteration of capillaries by fibrotic reactions was observed. Thus decreased ACE activity accompanies radiation-induced hypoperfusion and endothelial ultrastructural changes in rat lung. All of these reactions precede the development of pulmonary fibrosis.
为了确定内皮功能障碍在放射性肺损伤发病机制中的作用，对大鼠右半胸单次暴露于25 Gy的60Coγ射线后1至150天内的肺血管紧张素转换酶（ACE）活性、动脉灌注和超微结构进行了检测。照射后前2周，照射侧右肺的动脉灌注增加，然后在照射后30天降至左肺值的约80%。照射侧肺的灌注持续下降，到90 - 150天时仅为未照射侧肺的40%。照射侧右肺的ACE活性在暴露后30天内无明显变化，之后降至左肺的72%。右肺的ACE活性在照射后30至90天稳步下降，然后在150天内维持在低于正常水平的20%的平台期。照射后1天可见血管周围和间质水肿，并持续30天。30天时内皮细胞出现泡状化、碎片化和基底膜增厚。间隔中有肥大细胞，但此时间质胶原未增加。暴露后90至150天，观察到纤维化反应导致毛细血管逐渐闭塞。因此，ACE活性降低伴随着大鼠肺放射性低灌注和内皮超微结构变化。所有这些反应都先于肺纤维化的发生。
