Vuorio E I, Makela J K, Vuorio T K, Poole A, Wagner J C
University of Turku, Department of Medical Biochemistry, Finland.
Br J Exp Pathol. 1989 Jun;70(3):305-15.
The activation of collagen synthesis during development of silicotic fibrosis was studied in rats exposed, in dusting chambers, to respirable SiO2 for periods of 2, 4, 6 or 12 months. Control animals were exposed similarly to clean air or TiO2. Development of fibrosis was followed by histological examination, measurement of lung weight and determination of lung collagen content (as hydroxyproline). A steady increase in lung weight and collagen content together with changes in cellularity and metabolic activity of the lungs, as ascertained by chemical determination of DNA and RNA, were measured in the lungs of the SiO2-exposed animals. Hybridization of total lung RNA, extracted at each time point, with cDNA probes specific for type I and type III procollagen mRNA levels showed that the development of fibrosis was associated with increased levels, as compared to age matched controls, of pulmonary procollagen mRNAs. Interestingly, the highest levels of procollagen mRNAs were observed in young (pretreatment control) animals, suggesting that during pulmonary development collagen metabolism in lungs is even greater than during development of fibrosis. In rats exposed to SiO2 the increase in type III procollagen mRNA occurred earlier than the increase in type I procollagen mRNAs. These observations demonstrate both age-dependent and silicosis-related changes in pulmonary procollagen mRNA levels. The results suggest that development of silicosis is associated with an altered capacity of the lungs to regulate collagen accumulation.
在粉尘暴露舱中，将大鼠暴露于可吸入的二氧化硅（SiO₂）中2、4、6或12个月，研究矽肺纤维化发展过程中胶原合成的激活情况。对照动物同样暴露于清洁空气或二氧化钛（TiO₂）中。通过组织学检查、测量肺重量以及测定肺胶原含量（以羟脯氨酸计）来跟踪纤维化的发展。在暴露于SiO₂的动物肺中，测量到肺重量和胶原含量稳步增加，同时通过化学测定DNA和RNA确定肺的细胞数量和代谢活性发生了变化。在每个时间点提取的全肺RNA与I型和III型前胶原mRNA水平特异性的cDNA探针杂交显示，与年龄匹配的对照相比，纤维化的发展与肺前胶原mRNA水平升高有关。有趣的是，在前处理对照的年轻动物中观察到前胶原mRNA的最高水平，这表明在肺发育过程中，肺中的胶原代谢甚至比纤维化发展过程中还要旺盛。在暴露于SiO₂的大鼠中，III型前胶原mRNA的增加比I型前胶原mRNA的增加更早出现。这些观察结果表明肺前胶原mRNA水平存在年龄依赖性和矽肺相关的变化。结果表明，矽肺的发展与肺调节胶原积累的能力改变有关。
