Cocci Franca, Miniati Massimo, Monti Simonetta, Cavarra Eleonora, Gambelli Federica, Battolla Luigi, Lucattelli Monica, Lungarella Giuseppe
Istituto di Fisiologia Clinica del Consiglio Nazionale delle Ricerche (CNR), Area di Ricerca San Cataldo, Via Moruzzi 1, 56126, Pisa, Italy.
Int J Biochem Cell Biol. 2002 Jun;34(6):594-604. doi: 10.1016/s1357-2725(02)00015-8.
An enhanced proteolysis of lung interstitium is key event in the pathogenesis of emphysema, a major constituent of chronic obstructive pulmonary disease. To assess whether urinary desmosine and/or hydroxyproline may be used as a marker of lung destruction we studied urinary excretions of these products in 20 patients with chronic obstructive pulmonary disease and in 19 appropriate controls in 24h urine collection samples. For desmosine measurements, we developed a new indirect competitive enzyme-linked immunosorbent assay. The extent of emphysema was measured in high resolution computed tomography (CT) scans, by considering lung area with CT numbers <-950 Hounsfield units (HU). Urinary desmosine excretion was significantly higher in patients with chronic obstructive pulmonary disease than in controls (294+/-121 microg versus 183+/-93 microg, P=0.003), and was unrelated with both age and smoking habits. In patients with no evidence or only mild emphysema, desmosine excretion values were significantly higher (P=0.006) than those of patients with moderate to severe emphysema. In patients with chronic obstructive pulmonary disease, urinary hydroxyproline excretion was positively correlated with urinary desmosine excretion but on the average, it was not different from that of controls. These data indicate that urinary desmosine is a sensitive biological marker of lung elastin catabolism. The relatively low levels of urinary desmosine observed in patients with severe emphysema may be accounted for a decrease in elastin catabolism due to reduced lung elastin mass. Urinary desmosine may be used to identify subjects at risk of developing emphysema and to assess the efficacy of therapeutic interventions.
肺间质蛋白水解增强是肺气肿发病机制中的关键事件，肺气肿是慢性阻塞性肺疾病的主要组成部分。为了评估尿中锁链素和/或羟脯氨酸是否可作为肺破坏的标志物，我们在24小时尿液收集样本中研究了20例慢性阻塞性肺疾病患者和19例合适对照者这些产物的尿排泄情况。对于锁链素测量，我们开发了一种新的间接竞争酶联免疫吸附测定法。通过考虑CT值<-950亨氏单位（HU）的肺区域，在高分辨率计算机断层扫描（CT）中测量肺气肿的程度。慢性阻塞性肺疾病患者的尿锁链素排泄显著高于对照组（294±121微克对183±93微克，P = 0.003），且与年龄和吸烟习惯均无关。在无肺气肿证据或仅有轻度肺气肿的患者中，锁链素排泄值显著高于中度至重度肺气肿患者（P = 0.006）。在慢性阻塞性肺疾病患者中，尿羟脯氨酸排泄与尿锁链素排泄呈正相关，但平均而言，与对照组无差异。这些数据表明尿锁链素是肺弹性蛋白分解代谢的敏感生物标志物。在重度肺气肿患者中观察到的相对较低的尿锁链素水平可能是由于肺弹性蛋白量减少导致弹性蛋白分解代谢降低所致。尿锁链素可用于识别有发生肺气肿风险的个体，并评估治疗干预的疗效。
