Houben Joyce M J, Mercken Evi M, Ketelslegers Hans B, Bast Aalt, Wouters Emiel F, Hageman Geja J, Schols Annemie M W J
Department of Health Risk Analysis and Toxicology, University of Maastricht, The Netherlands.
Respir Med. 2009 Feb;103(2):230-6. doi: 10.1016/j.rmed.2008.09.003. Epub 2008 Oct 21.
Chronic oxidative stress and systemic inflammation contribute to the pathology of several chronic diseases, one among which is chronic obstructive pulmonary disease (COPD). In addition, increased oxidative stress and inflammation have been observed to be negatively associated with telomere length (TL). Our aim was to investigate the TL in COPD patients in relation to pulmonary and extrapulmonary disease severity. Furthermore, based on experimental evidence suggesting the effects of oxidative stress on telomere shortening, we studied the association of TL with the antioxidant enzyme superoxide dismutase (SOD). One hundred and two COPD patients with moderate to severe COPD were studied and compared with 19 healthy age-matched controls. Patients were characterized by elevated levels of inflammatory markers (CRP, sTNF-receptors) and lower SOD-activity than the controls (p<0.001), irrespective of the SOD genotype. TL was negatively associated with age (p<0.01) and was significantly shorter in COPD patients than controls (p<0.05). Within the patient group age-adjusted TL variability could not be explained by lung function and smoking history but a modest association was found with the percentage of fat mass (p<0.05). These data provide evidence for a relationship between a disturbed oxidant/antioxidant balance and telomere shortening and indicate that preservation of fat mass may be protective in delaying telomere shortening in COPD patients.
慢性氧化应激和全身炎症促成了多种慢性疾病的病理过程，其中之一就是慢性阻塞性肺疾病（COPD）。此外，研究发现氧化应激和炎症增加与端粒长度（TL）呈负相关。我们的目的是研究COPD患者的端粒长度与肺部及肺外疾病严重程度之间的关系。此外，基于氧化应激对端粒缩短影响的实验证据，我们研究了端粒长度与抗氧化酶超氧化物歧化酶（SOD）之间的关联。我们对102例中重度COPD患者进行了研究，并与19名年龄匹配的健康对照者进行比较。无论SOD基因型如何，患者的炎症标志物（CRP、sTNF受体）水平均升高，且SOD活性低于对照组（p<0.001）。端粒长度与年龄呈负相关（p<0.01），COPD患者的端粒长度明显短于对照组（p<0.05）。在患者组中，经年龄调整后的端粒长度变异性无法用肺功能和吸烟史来解释，但与体脂百分比存在适度关联（p<0.05）。这些数据为氧化/抗氧化平衡紊乱与端粒缩短之间的关系提供了证据，并表明保持体脂可能对延缓COPD患者的端粒缩短具有保护作用。
