Nagai A, Matsumiya H, Yasui S, Aoshiba K, Ishihara Y, Konno K
First Department of Medicine, Hygiene and Public Health, Tokyo Women's Medical College, Japan.
Exp Lung Res. 1993 Mar-Apr;19(2):203-19. doi: 10.3109/01902149309031720.
The purpose of this study was to examine how lungs in early postnatal animals that are administered bromodeoxyuridine (BrdU), a thymidine analog known to be a cytogenetically toxic agent, change in adult life. BrdU was injected (1 mg/g body weight) intraperitoneally in suckling rats on day 6 after birth. Immunohistochemical studies revealed that BrdU was incorporated in alveolar cells, and infrequently in the mesothelium, endothelium, and bronchiolar epithelium. The number (per high-power field) of alveolar cells incorporating BrdU was 8.76 +/- 0.50 in the interstitium and 1.66 +/- 0.25 in the epithelium. The animals were sacrificed at 2 and 8 weeks and 12 months of age. Control animals were treated the same as the BrdU-treated animals except for the injection of BrdU. Body weight, body size (nose-tail length), and lung weight were identical between BrdU-treated animals and control animals at all experimental periods. The histopathology and physiology of these lungs were studied. At 2 weeks of age, the BrdU-treated animals appeared morphologically and functionally similar to control animals. At 8 weeks and 12 months of age, the lungs in the BrdU-treated animals showed abnormal enlargement of the airspace, few alveoli, and less complexity in pulmonary architecture with or without increased lung compliance. These findings suggest that lung injured cytogenetically in early postnatal life may develop functional and structural abnormalities in later life.
本研究的目的是检测出生后早期接受溴脱氧尿苷（BrdU）（一种已知的细胞遗传学毒性剂，胸腺嘧啶核苷类似物）处理的动物肺脏在成年后的变化情况。在出生后第6天，给乳鼠腹腔注射BrdU（1毫克/克体重）。免疫组织化学研究显示，BrdU掺入肺泡细胞，很少掺入间皮、内皮和细支气管上皮。在间质中，每高倍视野掺入BrdU的肺泡细胞数量为8.76±0.50，在上皮中为1.66±0.25。在动物2周、8周和12月龄时将其处死。对照动物的处理方式与接受BrdU处理的动物相同，只是不注射BrdU。在所有实验阶段，接受BrdU处理的动物与对照动物的体重、体长（鼻尾长）和肺重量均相同。对这些肺脏的组织病理学和生理学进行了研究。在2周龄时，接受BrdU处理的动物在形态和功能上与对照动物相似。在8周龄和12月龄时，接受BrdU处理的动物的肺脏出现气腔异常扩大、肺泡较少以及肺结构复杂性降低，无论肺顺应性是否增加。这些发现表明，出生后早期受到细胞遗传学损伤的肺脏在后期生活中可能会出现功能和结构异常。
