Merrilees Mervyn J, Ching Pamela S T, Beaumont Brent, Hinek Aleksander, Wight Thomas N, Black Peter N
Department of Anatomy with Radiology, Faculty of Medical and Health Sciences, The University of Auckland, Auckland, New Zealand.
Respir Res. 2008 May 18;9(1):41. doi: 10.1186/1465-9921-9-41.
COPD is characterised by loss of alveolar elastic fibers and by lack of effective repair. Elastic fibers are assembled at cell surfaces by elastin binding protein (EBP), a molecular chaperone whose function can be reversibility inhibited by chondroitin sulphate of matrix proteoglycans such as versican. This study aimed to determine if alveoli of patients with mild to moderate COPD contained increased amounts of versican and a corresponding decrease in EBP, and if these changes were correlated with decreases in elastin and FEV1.
Lung samples were obtained from 26 control (FEV1 > or = 80% predicted, FEV1/VC >0.7) and 17 COPD patients (FEV1 > or = 40% - <80% predicted, FEV1/VC < or = 0.7) who had undergone a lobectomy for bronchial carcinoma. Samples were processed for histological and immuno-staining. Volume fractions (Vv) of elastin in alveolar walls and alveolar rims were determined by point counting, and versican and EBP assessed by grading of staining intensities.
Elastin Vv was positively correlated with FEV1 for both the alveolar walls (r = 0.66, p < 0.001) and rims (r = 0.41, p < 0.01). Versican was negatively correlated with FEV1 in both regions (r = 0.30 and 0.32 respectively, p < 0.05), with the highest staining intensities found in patients with the lowest values for FEV1. Conversely, staining intensities for EBP in alveolar walls and rims and were positively correlated with FEV1 (r = 0.43 and 0.46, p < 0.01).
Patients with mild to moderate COPD show progressively increased immuno-staining for versican and correspondingly decreased immuno-staining for EBP, with decreasing values of FEV1. These findings may explain the lack of repair of elastic fibers in the lungs of patients with moderate COPD. Removal of versican may offer a strategy for effective repair.
慢性阻塞性肺疾病（COPD）的特征是肺泡弹性纤维丧失且缺乏有效的修复。弹性纤维由弹性蛋白结合蛋白（EBP）在细胞表面组装而成，EBP是一种分子伴侣，其功能可被诸如多功能蛋白聚糖等基质蛋白聚糖的硫酸软骨素可逆性抑制。本研究旨在确定轻至中度COPD患者的肺泡中多功能蛋白聚糖含量是否增加以及EBP相应减少，以及这些变化是否与弹性蛋白和第一秒用力呼气容积（FEV1）的降低相关。
从26名对照者（FEV1≥预测值的80%，FEV1/用力肺活量（VC）>0.7）和17名因支气管癌接受肺叶切除术的COPD患者（FEV1≥预测值的40% - <80%，FEV1/VC≤0.7）获取肺样本。样本进行组织学和免疫染色处理。通过点计数法测定肺泡壁和肺泡边缘弹性蛋白的体积分数（Vv），并通过染色强度分级评估多功能蛋白聚糖和EBP。
肺泡壁和边缘的弹性蛋白Vv与FEV1均呈正相关（分别为r = 0.66，p < 0.001和r = 0.41，p < 0.01）。两个区域的多功能蛋白聚糖与FEV1均呈负相关（分别为r = 0.30和0.32，p < 0.05），FEV1值最低的患者染色强度最高。相反，肺泡壁和边缘EBP的染色强度与FEV1呈正相关（r = 0.43和0.46，p < 0.01）。
轻至中度COPD患者的多功能蛋白聚糖免疫染色逐渐增加，EBP免疫染色相应减少，同时FEV1值降低。这些发现可能解释了中度COPD患者肺中弹性纤维缺乏修复的原因。去除多功能蛋白聚糖可能提供一种有效修复的策略。
