Department of Respiratory Medicine, NUTRIM School for Nutrition, Toxicology and Metabolism, Maastricht University Medical Center, Maastricht, The Netherlands.
Eur J Clin Invest. 2012 Aug;42(8):807-14. doi: 10.1111/j.1365-2362.2012.02646.x. Epub 2012 Jan 31.
Chronic obstructive pulmonary disease (COPD) is associated with systemic inflammation and oxidative stress. N(ε) -(carboxymethyl) lysine (CML), an advanced glycation end product (AGE) and the soluble decoy receptor, sRAGE, are exciting new molecules linked to oxidative stress and inflammation. Here the levels of plasma sRAGE and CML were determined and their variation in relation to lung function, external long-term oxygen therapy (LTOT) and plasma levels of inflammatory molecules in COPD evaluated.
Plasma sRAGE and CML levels were measured by ELISA in 146 patients with stable COPD and 81 healthy subjects, subgrouped from a larger case-control study and matched for age, gender and pack-years smoked.
Decreased levels of plasma sRAGE and no significant difference in levels of plasma CML were found in patients with COPD in comparison with controls. In the total group, plasma sRAGE was positively associated with FEV(1) and forced vital capacity and negatively with pack-years smoked. In patients receiving LTOT, levels of plasma sRAGE were lower compared with those without LTOT. Only in controls, a weak correlation was found between plasma sRAGE and CML. sRAGE did not correlate with measured inflammatory markers, whereas CML was negatively correlated with fibrinogen.
Plasma sRAGE levels are lower in patients with COPD compared with healthy control subjects, and even lower levels in patients receiving LTOT. Because sRAGE correlated with lung function only in the whole group, sRAGE can be considered a marker of COPD, but not of disease severity. A lack of clear association between sRAGE, CML and systemic inflammation is furthermore evident.
慢性阻塞性肺疾病(COPD)与全身炎症和氧化应激有关。N(ε)-(羧甲基)赖氨酸(CML),一种糖化终产物(AGE)和可溶性诱饵受体 sRAGE,是与氧化应激和炎症有关的令人兴奋的新分子。本研究测定了血浆 sRAGE 和 CML 的水平,并评估了它们与肺功能、长期外部氧疗(LTOT)和 COPD 患者血浆炎症分子水平的变化。
通过 ELISA 法测定了 146 例稳定期 COPD 患者和 81 例健康对照者的血浆 sRAGE 和 CML 水平,这些患者来自一项较大的病例对照研究,按照年龄、性别和吸烟包年数进行匹配。
与对照组相比,COPD 患者的血浆 sRAGE 水平降低,而 CML 水平无显著差异。在总组中,血浆 sRAGE 与 FEV1 和用力肺活量呈正相关,与吸烟包年数呈负相关。在接受 LTOT 的患者中,血浆 sRAGE 水平低于未接受 LTOT 的患者。仅在对照组中,血浆 sRAGE 与 CML 之间存在弱相关性。sRAGE 与所测炎症标志物无相关性,而 CML 与纤维蛋白原呈负相关。
与健康对照组相比,COPD 患者的血浆 sRAGE 水平较低,而接受 LTOT 的患者的水平更低。由于 sRAGE 仅在整个组中与肺功能相关,因此 sRAGE 可以被认为是 COPD 的标志物,但不是疾病严重程度的标志物。sRAGE、CML 与全身炎症之间缺乏明确的关联也是显而易见的。