Franko A J, Sharplin J
Department of Radiation Oncology, Cross Cancer Institute, Edmonton, Alberta, Canada.
Radiat Res. 1994 Dec;140(3):347-55.
The development of lung fibrosis after single-dose thoracic irradiation was studied histologically in C57L/J male mice. Lung function was monitored using uptake of carbon monoxide. During the latent period (prior to 15 weeks postirradiation) mice were chosen at random, while during the early phase (15-22 weeks) mice were sacrificed when they developed a functional deficit of at least 50%. Excess mice with a deficit of 50% in the early phase were followed into the late phase and sacrificed at 31 or 40 weeks. Two scoring methods were used to quantify lung damage. Fibrotic lesions and foci of inflammation were counted for the latent period, and the proportion of nonfunctional acini was determined for the early and late phases. After a dose 1 Gy less than the LD50/180, small regions of mild inflammatory infiltration appeared at 6 weeks, and small, focal fibrotic lesions containing numerous macrophages appeared at 8 weeks postirradiation. The number of fibrotic lesions increased steadily during the latent period in a manner that is consistent with conversion of inflammatory lesions to foci of fibrosis. Mice sacrificed upon developing a 50% functional deficit during the early phase had approximately equal proportions of lung affected by fibrosis and inflammation. Those mice which developed a similar respiratory deficit in the early phase and were followed into the late phase usually showed little change in lung function. However, when sacrificed at 31 weeks they had twice as much fibrosis and very little inflammation, suggesting that the inflammatory lesions had become fibrosed. The average number of macrophages per unit area of fibrosis declined during the latent period and changed little during the early and late phases. Lymphocytes and mast cells were also quantified in fibrosed regions.
在C57L/J雄性小鼠中，通过组织学方法研究了单次胸部照射后肺纤维化的发展情况。使用一氧化碳摄取量来监测肺功能。在潜伏期（照射后15周之前）随机选择小鼠，而在早期阶段（15 - 22周），当小鼠出现至少50%的功能缺陷时将其处死。早期阶段功能缺陷达50%的多余小鼠进入后期阶段，并在31周或40周时处死。使用两种评分方法对肺损伤进行量化。在潜伏期计算纤维化病变和炎症灶的数量，在早期和后期确定无功能腺泡的比例。给予低于LD50/180 1 Gy的剂量后，6周时出现小面积轻度炎症浸润，照射后8周出现含有大量巨噬细胞的小灶性纤维化病变。在潜伏期，纤维化病变的数量以与炎症病变转化为纤维化灶一致的方式稳步增加。在早期阶段出现50%功能缺陷时处死的小鼠，肺受纤维化和炎症影响的比例大致相等。那些在早期阶段出现类似呼吸功能缺陷并进入后期阶段的小鼠，肺功能通常变化不大。然而，在31周处死时，它们的纤维化程度是原来的两倍，炎症很少，这表明炎症病变已纤维化。在潜伏期，每单位面积纤维化区域内巨噬细胞的平均数量下降，在早期和后期变化不大。还对纤维化区域的淋巴细胞和肥大细胞进行了定量分析。
