Wijnhoven J H, Hafmans T, Dekhuijzen P N R
Department of Pulmonary Diseases and Institute for Fundamental and Clinical Human Movement Sciences, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.
Respiration. 2006;73(4):529-37. doi: 10.1159/000091270. Epub 2006 Jan 30.
Chronic obstructive pulmonary disease (COPD) is associated with an increased load on the diaphragm. Increased (eccentric) loading has been shown to result in disturbances in the cytoskeleton.
We hypothesized that due to a continuous overload of the diaphragm in COPD patients, distinct alterations in the membrane-associated cytoskeleton occur, especially in the costameres.
Diaphragm biopsies from 7 COPD patients (forced expiratory volume in 1 s 62 +/- 3% predicted) and 5 non-COPD patients (forced expiratory volume in 1 s 105 +/- 6% predicted) were obtained. Cryosections of these biopsies were stained with antibodies against the costameric proteins of the focal adhesion complex (vinculin, talin and integrin-beta(1)), the dystroglycan complex (dystrophin and beta-dystroglycan) and the spectrin-based membrane cytoskeleton (beta-spectrin). Furthermore, in these cryosections, the basal membrane protein laminin was stained.
We found no differences in the distribution and staining intensity of the costameric proteins of the focal adhesion complex, the dystroglycan complex and the spectrin-based membrane cytoskeleton in the diaphragm between the COPD and the non-COPD patients. Furthermore, no differences were observed in the expression of laminin in the diaphragm between COPD and non-COPD patients.
These results indicate that the increased loading to which the diaphragm is exposed in COPD does not result in disturbances in expression of the costameric system and histological damage of the sarcolemma.
慢性阻塞性肺疾病（COPD）与膈肌负荷增加有关。已表明增加的（离心）负荷会导致细胞骨架紊乱。
我们假设，由于COPD患者膈肌持续过载，膜相关细胞骨架会出现明显改变，尤其是在肌小节。
获取7例COPD患者（第1秒用力呼气量为预测值的62±3%）和5例非COPD患者（第1秒用力呼气量为预测值的105±6%）的膈肌活检样本。这些活检样本的冰冻切片用针对粘着斑复合体（纽蛋白、踝蛋白和整合素-β1）、肌营养不良聚糖复合体（肌营养不良蛋白和β-肌营养不良聚糖）以及基于血影蛋白的膜细胞骨架（β-血影蛋白）的肌小节蛋白的抗体进行染色。此外，在这些冰冻切片中，对基底膜蛋白层粘连蛋白进行染色。
我们发现COPD患者和非COPD患者膈肌中粘着斑复合体、肌营养不良聚糖复合体以及基于血影蛋白的膜细胞骨架的肌小节蛋白的分布和染色强度没有差异。此外，COPD患者和非COPD患者膈肌中层粘连蛋白的表达也没有差异。
这些结果表明，COPD患者膈肌所承受的增加负荷不会导致肌小节系统表达紊乱和肌膜组织学损伤。
