慢性阻塞性肺疾病患者膈肌组织学改变及一氧化氮合酶表达变化的研究

目的 探讨慢性阻塞性肺疾病(COPD)患者膈肌组织学改变的特点和内源性一氧化氮合酶的表达变化.以及COPD患者膈肌功能异常可能的机制.方法 对19例患肺部或食管肿瘤行开胸手术的患者,其中12例轻、中度COPD患者,7例肺功能正常对照者留取膈肌样本.观察膈肌超微结构的改变、并测定膈肌肌球蛋白重链(MHC)表型、肌纤维横截...

Diaphragm alteration and nitric oxide synthases expression in chronic obstructive pulmonary disease

Objective To investigate the histological alterations and the diaphragmatic expression of nitric oxide synthases (NOS) in the patients with mild-moderate chronic obstructive pulmonary disease (COPD), and to clarify the possible mechanisms of diaphragm contractile dysfunction in COPD. Methods 19 male patients undergoing thoracotomy for localized lung or esophagus neoplasm were selected for the study, 12 of them with stable mild-moderate COPD and 7 with normal pulmonary function. Diaphragm ultrastructure injuries were observed by electron microscopy. MHC isoform,cross section area (CSA) of diaphragm fibers, and the location of NOS expression in diaphragm were measured by immunohistochemistry, Western blotting was used to analyze the expression of NOS and Nitrotyrosine (NT) proteins. BMI and albumin were measured to evaluate the nutritional status, and the pulmonary function was measured before surgery. Results ?Signs of sarcomeres disruption and Z-band streaming were observed in the diaphragm of the patients with mild and moderate COPD. In addition, mitochondria of MHC isoforms were no difference between the two groups ( P＞0. 05). The CSA of the different MHC isoforms of diaphragm did not differ between the two groups, while taken the moderate COPD patients as a single group, the CSA of muscles expressed MHCslow were decreased compared with the control group ( P ＜0. 05). Compared with the control group, MHC protein expression in COPD group was significantly group, nNOS and iNOS were significantly higher in COPD group ( P＜0. 05), but eNOS expression did not differ between the two groups ( P ＞0. 05). NT expression was significantly higher compared with the control group ( P ＜0. 05). The level of nNOS isoforms and NT were inversely correlated with FEV1 %predicted. Conclusions The ultrastructure injuries and muscle atrophy occurred in the diaphragm of COPD. Endogenous NOS of diaphragm was increased significantly, which induced the increase of nitrate tyrosine. These alterations may contribute to the diaphragm dysfunction in the patients with COPD.