Reiser K M, Last J A
Am Rev Respir Dis. 1981 Jan;123(1):58-63. doi: 10.1164/arrd.1981.123.1.58.
Changes in collagen metabolism were examined in 3 models of acute respiratory disease in rats. Fibrotic changes in the lungs of rats were provoked by exposing them to paraquat (intraperitoneal), ozone (inhaled), or bleomycin (intratracheally injected). After an interval sufficient to allow histologically discernible fibrosis to occur (6 to 7 days), lungs were removed from the rats, and apparent collagen synthesis rates were determined with cultured lung minces incubated in medium containing 3H-proline. There was a significant increase (severalfold in the apparent collagen synthesis rates by lung minces from all the pneumotoxin-exposed rats in this study. Portions of the 3H-proline-labeled lung minces were then used for quantifying ratios of Type I to Type III collagen. Using CNBr mapping techniques and a combination of carboxymethylcellulose chromatography and polyacrylamide gel electrophoresis, we quantified Type I/Type III collagen for newly synthesized, 3H-labeled collagen as well as for total unlabeled collagen. In lung minces from normal rats, the ratio was 2:1 (65 to 70% Type I collagen) for both newly synthesized and total collagen. On the other hand, lung minces prepared from fibrotic rats accumulated a mixture of newly synthesized collagens that was substantially enriched for Type I collagen (80 to 85% Type I). There was no change in Type I/Type III collagen for total unlabeled collagen, nor was there any detectable increase of total collagen per lung after 1 wk. We conclude that an early event in experimental acute respiratory disease is a marked increase in the relative synthesis of Type I collagen; this shift occurs before there is observable increased accumulation of collagen in the lung.
在大鼠的三种急性呼吸道疾病模型中研究了胶原代谢的变化。通过给大鼠腹腔注射百草枯、吸入臭氧或气管内注射博来霉素，诱发大鼠肺部的纤维化改变。在经过足以使组织学上可辨别的纤维化出现的间隔时间（6至7天）后，从大鼠身上取出肺脏，并用含有3H-脯氨酸的培养基培养肺组织小块，测定其表观胶原合成速率。在本研究中，所有接触肺毒素的大鼠的肺组织小块的表观胶原合成速率均显著增加（增加了几倍）。然后，将部分3H-脯氨酸标记的肺组织小块用于定量I型胶原与III型胶原的比例。使用溴化氰图谱技术以及羧甲基纤维素层析和聚丙烯酰胺凝胶电泳相结合的方法，我们对新合成的、3H标记的胶原以及总的未标记胶原的I型/III型胶原进行了定量。在正常大鼠的肺组织小块中，新合成的胶原和总胶原的比例均为2:1（I型胶原占65%至70%）。另一方面，从纤维化大鼠制备的肺组织小块积累了新合成的胶原混合物，其中I型胶原显著富集（I型胶原占80%至85%）。总未标记胶原的I型/III型胶原比例没有变化，并且在1周后每只肺的总胶原也没有可检测到的增加。我们得出结论，实验性急性呼吸道疾病的早期事件是I型胶原相对合成的显著增加；这种转变发生在肺中可观察到的胶原积累增加之前。
