REGULATION OF LUNG FIBROBLAST PROLIFERATION AND PROTEIN-SYNTHESIS BY BRONCHIOLAR LAVAGE IN EXPERIMENTAL SILICOSIS
REGULATION OF LUNG FIBROBLAST PROLIFERATION AND PROTEIN-SYNTHESIS BY BRONCHIOLAR LAVAGE IN EXPERIMENTAL SILICOSIS
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DOI：
10.1016/s0013-9351(86)80168-2
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发表时间：
1986-10-01
影响因子：
8.3
通讯作者：
SCHEVE, LG
中科院分区：
文献类型：
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作者：
BENSON, SC;BELTON, JC;SCHEVE, LG
对雄性 Sprague-Dawley 大鼠进行单次气管内滴注 30 mg Min-U-Sil 二氧化硅的无菌盐水，并在滴注后 3、7 或 14 天处死。对照动物仅滴注无菌盐水。二氧化硅滴注产生炎症反应，随后出现肺纤维化特征的组织学变化。在接触二氧化硅的动物中检测到与炎症细胞转化为大的多灶性纤维化结节相关的增厚的肺泡间隔。从注入二氧化硅的动物获得的灌洗液中检测到支气管肺泡细胞（主要是巨噬细胞）数量增加，蛋白质（主要是血清白蛋白）水平升高，溶菌酶、蛋白水解酶（胰蛋白酶样）和髓过氧化物酶活性升高。这些因素（溶菌酶活性除外）在滴注后 3 至 7 天升高至高于对照水平，并在第 14 天降至接近对照水平。在滴注后 3 天和 7 天，二氧化硅处理的大鼠肺组织碎屑中 DNA、胶原蛋白和非胶原蛋白的合成率显着升高。损伤后 9 周观察到总蛋白水平升高，尤其是肺胶原蛋白水平升高。注入二氧化硅的大鼠灌洗液刺激增殖和静止大鼠肺成纤维细胞培养物中的 DNA 合成。注入二氧化硅的大鼠的灌洗液也会刺激肺成纤维细胞，增加胶原蛋白和非胶原蛋白的合成。
Male Sprague-Dawley rats were subjected to single, intratracheal instillation of 30 mg Min-U-Sil silica in sterile saline and were sacrificed 3, 7, or 14 days following instillation. Control animals were instilled with sterile saline only. Silica instillation produced an inflammatory reaction followed by histological changes characteristic of lung fibrosis. Thickened alveolar septa associated with inflammatory cells transforming into large multifocal fibrotic nodule were detected in silica-exposed animals. Increased numbers of bronchoalveolar cells (principally macrophages), elevated levels of protein (principally serum albumin), and lysozyme, proteolytic (trypsin-like), and myeloperoxidase activities were detected in lavage fluids obtained from animals instilled with silica. These factors (except for lysozyme activity) were elevated above control levels from 3 to 7 days postinstillation and declined to near control levels by Day 14. The rate of DNA, collagen, and noncollagen protein synthesis was significantly elevated in lungs tissue minces from silica-treated rats 3 and 7 days fter instillation. Elevated levels of total protein, and lung collagen in particular, were observed 9 weeks after insult. Lavage fluid from silica-instilled rats stimulus DNA synthesis in cultures of proliferating and quiescent rat lung fibroblasts. Lavage fluids from silica-instilled rats also stimulates lung fibroblast to increase collagen and noncollagen protein synthesis.