CAJ | 학술논문

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、肌纤维横截面积、一氧化氮合酶及亚硝基酪氨酸(NT)的变化.同时,检测体质量指数、白蛋白水平及肺功能.结果 ①透射电镜示COPD组膈肌肌丝排列紊乱及断裂,Z线模糊,A带和I带破坏、结构消失,线粒体呈簇状分布,并伴有髓样变;②与对照组相比,COPD 组膈肌MHC亚型表达无变化(P＞0.05),中度COPD表达MHC慢收缩的膈肌纤维横截面积明显降低(P＜0.05);COPD组膈肌MHC蛋白表达降低(P＜0.05),并与FEV1%pred呈正相关;③与对照组相比,COPD组膈肌神经元型一氧化氮合酶和诱导型一氧化氮合酶表达明显升高(P＜0.05),而内皮型一氧化氮合酶表达无变化(P＞0.05),NT表达明显升高(P＜0.05);一氧化氮合酶和NT表达均与FEV1%pred呈负相关.结论早期COPD患者即出现膈肌超微结构损伤及肌萎缩,此改变在中度COPD时更明显;轻、中度COPD患者膈肌纤维无明显移行性改变;膈肌内源性NO生成增多,同时膈肌蛋白亚硝基化作用增强,这些改变均可能导致COPD患者膈肌收缩功能异常.
목적 탐토만성조새성폐질병(COPD)환자격기조직학개변적특점화내원성일양화담합매적표체변화.이급COPD환자격기공능이상가능적궤제.방법 대19례환폐부혹식관종류행개흉수술적환자,기중12례경、중도COPD환자,7례폐공능정상대조자류취격기양본.관찰격기초미결구적개변、병측정격기기구단백중련(MHC)표형、기섬유횡절면적、일양화담합매급아초기락안산(NT)적변화.동시,검측체질량지수、백단백수평급폐공능.결과 ①투사전경시COPD조격기기사배렬문란급단렬,Z선모호,A대화I대파배、결구소실,선립체정족상분포,병반유수양변;②여대조조상비,COPD 조격기MHC아형표체무변화(P＞0.05),중도COPD표체MHC만수축적격기섬유횡절면적명현강저(P＜0.05);COPD조격기MHC단백표체강저(P＜0.05),병여FEV1%pred정정상관;③여대조조상비,COPD조격기신경원형일양화담합매화유도형일양화담합매표체명현승고(P＜0.05),이내피형일양화담합매표체무변화(P＞0.05),NT표체명현승고(P＜0.05);일양화담합매화NT표체균여FEV1%pred정부상관.결론 조기COPD환자즉출현격기초미결구손상급기위축,차개변재중도COPD시경명현;경、중도COPD환자격기섬유무명현이행성개변;격기내원성NO생성증다,동시격기단백아초기화작용증강,저사개변균가능도치COPD환자격기수축공능이상.
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.