Jones A W, Reeve N L
J Pathol. 1978 Apr;124(4):227-33. doi: 10.1002/path.1711240407.
The pulmonary changes produced in mice given bleomycin intraperitoneally (twice weekly for 4 weeks, total dose 240 mg/kg) were examined by light and electron microscopy. Bleomycin damaged the pulmonary vessels and produced type I pneumocyte necrosis, resulting in non-uniform pulmonary fibrosis. The sequence of events leading to pulmonary fibrosis may be arbitrarily divided into three phases: firstly, a focal perivascular lesion consisting of interstitial oedema with plasma cell and lymphocyte infiltration; followed by the middle proliferative phase characterised by type I pneumocyte necrosis, intra-alveolar fibrin deposition, an increase in the numbers of type II pneumocytes and fibroblasts and an overall decrease in the alveolar diameter. The third phase consisted of organisation, with intra-alveolar and interstitial collagen formation and the synthesis of elastin. These phases, although occurring sequentially, did not bear a constant time relationship to the dosage schedule, for new early focal lesions continued to appear throughout the period of the experiment. These ultrastructural changes are not specific for bleomycin, but represent a general reaction of the lung to injury. The exact mechanism whereby bleomycin produces the lung damage has yet to be ascertained.
对腹腔注射博来霉素的小鼠（每周两次，共4周，总剂量240毫克/千克）肺部的变化进行了光镜和电镜检查。博来霉素损伤肺血管并导致I型肺细胞坏死，从而引起不均匀的肺纤维化。导致肺纤维化的一系列事件可任意分为三个阶段：首先，为局灶性血管周围病变，表现为间质水肿伴浆细胞和淋巴细胞浸润；其次是中间增殖期，其特征为I型肺细胞坏死、肺泡内纤维蛋白沉积、II型肺细胞和成纤维细胞数量增加以及肺泡直径总体减小。第三阶段为机化期，伴有肺泡内和间质胶原形成以及弹性蛋白合成。这些阶段虽然依次发生，但与给药方案并无固定的时间关系，因为在整个实验期间新的早期局灶性病变持续出现。这些超微结构变化并非博来霉素所特有，而是代表了肺对损伤的一般反应。博来霉素导致肺损伤的确切机制尚待确定。
