Reiser K M, Tryka A F, Lindenschmidt R C, Last J A, Witschi H R
Department of Internal Medicine, School of Medicine, University of California, Davis.
J Biochem Toxicol. 1986 Mar;1(1):83-91. doi: 10.1002/jbt.2570010109.
Collagen cross-linking was analyzed in lungs of rats, two, four, and ten weeks after intratracheal instillation of 1.5 units of bleomycin. Similar analyses were performed on lungs of mice 18 months after intratracheal instillation of bleomycin with or without subsequent exposure to 70% oxygen (O2) for 72 hours. Lungs were analyzed to determine the content of the reduced difunctional cross-links dihydroxylysinonorleucine (DHLNL) and hydroxylysinonorleucine (HLNL) and of the nonreducible trifunctional cross-link hydroxypyridinium (OHP). Ratios of DHLNL:HLNL were elevated in the rat lungs at two and four weeks, due to increased levels of DHLNL. There were no changes in the difunctional cross-links in any of the mouse lungs. Hydroxypyridinium content was elevated in the rat lungs at ten weeks and in the mouse lungs exposed to bleomycin and oxygen. We conclude that increases in DHLNL may serve as an early indicator that potentially "fibrotic collagen" is being synthesized in lungs acutely exposed to fibrogenic stimuli, while increases in OHP may serve as a permanent marker of a fibrogenic event that could have occurred months to years earlier.
在气管内注入1.5单位博来霉素后两周、四周和十周的大鼠肺中分析胶原交联情况。对气管内注入博来霉素后18个月的小鼠肺进行类似分析，部分小鼠随后暴露于70%氧气（O2）中72小时。分析肺组织以确定还原性双功能交联物二羟基赖氨酸正亮氨酸（DHLNL）和羟基赖氨酸正亮氨酸（HLNL）以及非还原性三功能交联物羟基吡啶鎓（OHP）的含量。由于DHLNL水平升高，大鼠肺在两周和四周时DHLNL:HLNL比值升高。任何小鼠肺中的双功能交联物均无变化。大鼠肺在十周时以及暴露于博来霉素和氧气的小鼠肺中羟基吡啶鎓含量升高。我们得出结论，DHLNL的增加可能作为一个早期指标，表明急性暴露于致纤维化刺激的肺中正在合成潜在的“纤维化胶原”，而OHP的增加可能作为一个纤维化事件的永久标志物，该事件可能在数月至数年之前就已发生。
