Cadieux A, Massé S, Sirois P
Environ Health Perspect. 1983 Sep;51:287-91. doi: 10.1289/ehp.8351287.
The measurement of pulmonary metabolism of three vasoactive substances and quantitative assessment of changes in lung morphology were performed in a long-term study of asbestos-exposed guinea pigs. Animals received intratracheal injections of a single dose of a sterile suspension of Canadian chrysotile B (5 mg), while control animals received only saline. Six months after the treatment, the guinea pigs were sacrificed, the lungs removed, perfused via the pulmonary artery and the metabolism of vasoactive substances was assessed (in vitro) in a cascade superfusion system. At the end of the experiments, the lungs were fixed in a glutaraldehyde solution for microscopic examination. The tissue response consisted of both inflammatory reaction of terminal and respiratory bronchioles and diffuse alveolar septal infiltration with interstitial fibrosis. The reaction was characterized at six months by a progressive bronchiolitis obliterans with fibroblastic proliferation and collagen formation. The development of the disease did not cause significant changes in the metabolism of acetylcholine and bradykinin. However, the metabolism of prostaglandin E2 decreased with the appearance of the bronchiolitis obliterans. Our results showed that asbestos exposure may produce early biochemical changes resulting in altered lung metabolism of vasoactive substances; these modifications could contribute to the pathogenesis of asbestosis.
在一项针对石棉暴露豚鼠的长期研究中，对三种血管活性物质的肺代谢进行了测量，并对肺形态变化进行了定量评估。动物接受气管内注射单剂量加拿大温石棉B无菌悬浮液（5毫克），而对照动物仅接受生理盐水。治疗六个月后，处死豚鼠，取出肺脏，通过肺动脉灌注，并在级联超灌注系统中（体外）评估血管活性物质的代谢。实验结束时，将肺脏固定在戊二醛溶液中进行显微镜检查。组织反应包括终末细支气管和呼吸性细支气管的炎症反应以及伴有间质纤维化的弥漫性肺泡间隔浸润。六个月时，反应的特征是进行性闭塞性细支气管炎伴成纤维细胞增殖和胶原形成。该疾病的发展并未导致乙酰胆碱和缓激肽代谢的显著变化。然而，随着闭塞性细支气管炎的出现，前列腺素E2的代谢降低。我们的结果表明，接触石棉可能会产生早期生化变化，导致血管活性物质的肺代谢改变；这些改变可能有助于石棉肺的发病机制。
