Lehnert B E, Dethloff L A, Finkelstein J N, van der Kogel A J
Los Alamos National Laboratory, NM.
Int J Radiat Biol. 1991 Oct;60(4):657-75. doi: 10.1080/09553009114552481.
The temporal patterns of several responses in the lungs of groups of rats administered two different thoracic doses of X-rays (7.5 and 15 Gy) were examined during a time frame within which radiation pneumonitis develops (1-13-week period) in order to assess for potential interrelationships among the responses. Endpoints surveyed included lung gravimetric and volumetric changes, changes in lavaged alveolar macrophage (AM) numbers, interstitial accumulations of mast cells (MC), and alterations in the amounts of lavaged phospholipids (PL), protein (P), and histamine (H). Sham-irradiated rats served as controls. Early (1 week), dose-dependent increases in lavageable PL were not accompanied by increases in lung weights or lavageable P. Elevations in lavaged PL continued for at least 5 weeks after exposure. By this time, lung weights, AM numbers, MC, and lavageable P, but not lavageable H, were all substantially increased in lungs that received the 15 Gy dose, whereas these changes were not observed at the lower dose. At later times (weeks 7 and 9), the hyperpermeability response following the 15 Gy exposure became less pronounced and the PL response also subsided, while lung MC continued to further increase and lavageable H became abnormally elevated. Maximal increases in the lung's permeability status after the 15 Gy exposure was coincidental with maximal increases in AM. An association of increases in AM and lung hyperpermeability, however, was not evident as of week 13 after the 7.5 Gy dose when lung weights and lavageable P were significantly elevated. For the X-ray doses examined, our results suggest that: (1) the early PL response to X-rays is independent of, and precedes, permeability changes in the lung; (2) the time to onset of an X-irradiation-induced increase in lung permeability is dose-dependent; (3) the progressive accumulation of MC in the lung following X-irradiation is dose-dependent; (4) excessive accumulations of interstitial MC after X-irradiation do not necessarily result in an increase in free H; and (5) free H in the lung does not appear to play a prominent role in the hyperpermeable response. Additionally, in conjunction with the findings of other investigators, our study suggests that the MC response to X-rays may be a fundamental component of the fibrogenic response.
为了评估不同反应之间的潜在相互关系，在放射性肺炎发生的时间段（1 - 13周）内，检查了给予两种不同胸部剂量X射线（7.5和15 Gy）的大鼠组肺部几种反应的时间模式。所调查的终点包括肺重量和体积变化、灌洗肺泡巨噬细胞（AM）数量变化、肥大细胞（MC）的间质积聚以及灌洗磷脂（PL）、蛋白质（P）和组胺（H）含量的改变。假照射大鼠作为对照。早期（1周），可灌洗PL的剂量依赖性增加并未伴随肺重量或可灌洗P的增加。暴露后，灌洗PL升高持续至少5周。此时，接受15 Gy剂量的肺中肺重量、AM数量、MC和可灌洗P均显著增加，但可灌洗H未增加，而在较低剂量时未观察到这些变化。在后期（第7周和第9周），15 Gy照射后的高通透性反应变得不那么明显，PL反应也减弱，而肺MC继续进一步增加，可灌洗H异常升高。15 Gy照射后肺通透性状态的最大增加与AM的最大增加同时发生。然而，在7.5 Gy剂量后第13周，当肺重量和可灌洗P显著升高时，AM增加与肺高通透性之间的关联并不明显。对于所检查的X射线剂量，我们的结果表明：（1）对X射线的早期PL反应独立于肺通透性变化且先于其发生；（2）X射线诱导的肺通透性增加的起始时间是剂量依赖性的；（3）X射线照射后肺中MC的逐渐积聚是剂量依赖性的；（4）X射线照射后间质MC的过度积聚不一定导致游离H增加；（5）肺中的游离H似乎在高通透性反应中不起主要作用。此外，结合其他研究者的发现，我们的研究表明MC对X射线的反应可能是纤维化反应的一个基本组成部分。
