LUNG COLLAGEN IN SILICOSIS: FIBROSIS MECHANISMS

实验性大鼠肺纤维化的研究进展 二氧化硅、博莱霉素、臭氧或百草枯提示， 硅肺不同于其他类型纤维化中的胶原代谢。 在 这个建议我计划研究胶原代谢的新方面， 矽肺病 具体来说，我建议进行详细调查， 肺胶原交联，使用体内标记结合新的HPLC 技术，在三组大鼠：对照组，大鼠暴露于二氧化硅， 暴露于博莱霉素的大鼠 要检查的参数包括类型和 每个胶原分子交联量、交联时间过程 交叉连接的形成、转换、交叉连接的减少和位置 的crosslink。 我假设特定的交联模式可能会 作为一种信号，决定胶原蛋白是否注定要成为 不可逆地沉积为“纤维化胶原蛋白”，或者它最终是否 注定要堕落。 我进一步假设肺胶原蛋白 硅肺动物中的交联将不同于在这两种动物中发现的交联。 正常和博莱霉素暴露的大鼠。 最后，我将使用数据库 从这些研究中得出的结论， 筛选检测指示早期硅肺变化。

Previous studies of experimental pulmonary fibrosis induced in rodents by silica, bleomycin, ozone, or paraquat suggest that collagen metabolism in silicosis differs from collagen metabolism in other types of fibrosis. In this proposal I plan to investigate new aspects of collagen metabolism in silicosis. Specifically, I propose to conduct a detailed investigation of lung collagen crosslinking, using in vivo labeling coupled with a new HPLC technique, in three groups of rats: controls, rats exposed to silica, and rats exposed to bleomycin. Parameters to be examined include type and amount of crosslink per collagen molecule, time course of crosslink formation, turnover of crosslinks, reducibility of crosslinks, and location of crosslinks. I hypothesize that specific crosslinking patterns may act as a kind of signal, determining whether the collagen is destined to become irreversibly deposited as "fibrosis collagen" or whether it is eventually destined for degradation. I further hypothesize that lung collagen crosslinking in silicotic animals will differ from that found in both normal and bleomycin-exposed rats. Finally, I will use the data base derived from these studies to guide the development of simple urine screening assays indicative of early silicotic changes.