EXPERIMENTAL BLEOMYCIN LUNG IN MICE - A CONTRIBUTION TO THE PATHOGENESIS OF PULMONARY FIBROSIS
EXPERIMENTAL BLEOMYCIN LUNG IN MICE - A CONTRIBUTION TO THE PATHOGENESIS OF PULMONARY FIBROSIS
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DOI：
10.1007/bf02713855
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发表时间：
1983-01-01
期刊：
影响因子：
5
通讯作者：
MORGENROTH, K
中科院分区：
文献类型：
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作者：
FASSKE, E;MORGENROTH, K
在 120 天的长期研究中，交错腹腔注射。将0.15-18mg剂量的细胞抑制多肽博来霉素给予NMRI小鼠以产生肺纤维化。通过光学显微镜和电子显微镜每隔 5 天监测一次肺部反应的发生和进展。根据形态学改变，推测肺纤维化的发病机制链：主要病变出现在肺泡毛细血管中，伴有内皮肿胀和间质水肿。肺泡壁增厚导致 II 型肺细胞反应性增殖，表面活性剂过量产生。由于表面活性剂在内肺泡表面的单分子扩散受到干扰，II 型肺泡细胞中形成巨大的层状体。这些 II 型细胞坏死，肺泡中存在的游离表面活性剂被单核肺泡巨噬细胞吞噬。巨噬细胞死亡并释放介质，激活成纤维细胞，导致原纤维形成。显然，肺纤维化过程中表面活性剂的持续产生和单核细胞从血流中的迁移一旦开始，就可以自我延续，即使在病因不再存在之后也是如此。
In long term studies over a period of 120 days, staggered i.p. 0.15-18 mg doses of the cytostatic polypeptide bleomycin were given to NMRI mice to produce pulmonary fibroses. The onset and progression of the lung reaction was monitored at 5-day intervals by light microscopy and EM. On the basis of the morphological alterations, a pathogenetic chain of events is postulated for pulmonary fibrosis: the primary lesions arise in the alveolar capillaries, with endothelial swelling and interstitial edema. Thickening of the alveolar wall leads to a reactive proliferation of type II pneumocytes with overproduction of surfactant. As a result of the disturbed monomolecular spreading of surfactant on the inner alveolar surface, giant lammellar bodies are formed in type II pneumocytes. These type II cells become necrotic, and free surfactant present in the alveoli is phagocytized by monocytic alveolar macrophages. The macrophages perish and release mediators which activate fibroblasts resulting in fibrillogenesis. Evidently, continuous production of surfactant and migration of monocytes from the blood stream the course of pulmonary fibrosis, once started, can be self-perpetuating, even after the etiological factor is no longer present.