Mariani T J, Roby J D, Mecham R P, Parks W C, Crouch E, Pierce R A
Department of Internal Medicine, Washington University School of Medicine at Jewish Hospital, St. Louis, Missouri 63110, USA.
Am J Pathol. 1996 Jan;148(1):151-64.
We have used the silica-induced model of pulmonary injury in the rat to study the pattern of collagen expression in granulomatous lung inflammation. A single intratracheal instillation of silica into adult rats resulted in granulomatous inflammation leading to fibrosis and alveolar proteinosis. The development of disease in these animals was characterized over a 27-day period after treatment by means of histological, biochemical, and molecular analyses. Biochemical analyses indicated that significant increases in the weights of silicotic lungs were due to elevated amounts of DNA and total protein. Analysis of hydroxyproline content showed a 15-fold increase in this amino acid in silicotic lungs, confirming the development of a fibrotic reaction. In situ hybridization for type I procollagen mRNA displayed increased gene expression in the parenchyma, conducting airways, and vasculature of silicotic rats. Within the parenchyma, type I procollagen was expressed uniquely within granulomatous lesions. Immunohistochemistry indicated type I procollagen was being expressed by an alpha-smooth muscle actin-negative population of cells. Immunolocalization of extra-cellular transforming growth factor-beta showed coincident temporal and spatial overlap with type I procollagen expression, implicating this cytokine as a mediator of collagen gene expression in this model.
我们利用大鼠二氧化硅诱导的肺损伤模型来研究肉芽肿性肺炎症中胶原蛋白的表达模式。将二氧化硅单次气管内注入成年大鼠会导致肉芽肿性炎症，进而引发纤维化和肺泡蛋白沉积症。通过组织学、生化和分子分析手段，对这些动物在治疗后27天内疾病的发展情况进行了表征。生化分析表明，硅肺重量的显著增加是由于DNA和总蛋白含量升高所致。羟脯氨酸含量分析显示，硅肺中这种氨基酸增加了15倍，证实了纤维化反应的发生。I型前胶原mRNA的原位杂交显示，硅肺大鼠的实质、传导气道和脉管系统中基因表达增加。在实质内，I型前胶原仅在肉芽肿性病变中表达。免疫组织化学表明，I型前胶原由α平滑肌肌动蛋白阴性的细胞群体表达。细胞外转化生长因子-β的免疫定位显示，其与I型前胶原表达在时间和空间上存在一致的重叠，表明该细胞因子在该模型中是胶原蛋白基因表达的介质。
