García-Valero José, Olloquequi Jordi, Rodríguez Esther, Martín-Satué Mireia, Texidó Laura, Ferrer Jaume
Department of Cell Biology, Physiology and Immunology, Faculty of Biology, University of Barcelona, Barcelona, Spain.
Laboratory of Cellular and Molecular Pathology, Instituto de Ciencias Biomédicas, Universidad Autónoma de Chile, Talca, Chile.
Arch Bronconeumol (Engl Ed). 2021 Jan 27. doi: 10.1016/j.arbres.2020.12.032.
The aim of this study is to analyze the expression of the main oxidant scavenger superoxide dismutase (EC-SOD), its main binding protein Fibulin-5 and several oxidative and nitrosative-derived products in the lung of COPD patients and controls.
Lung tissue samples from 19 COPD patients and 20 control subjects were analyzed. The architecture of elastic fibres was assessed by light and electron microscope histochemical techniques, and levels of EC-SOD and fibulin-5 were analyzed by immunohistochemistry and RT-PCR. The impact of oxidative stress on the extracellular matrix was estimated by immunolocalization of 4-hydroxynonenal (4-HNE), malondialdehyde (MDA) and 3-nitrotyrosine (3-NYT) adducts.
Alveolar walls of COPD patients exhibited abnormal accumulations of collapsing elastic fibres, showing a pierced pattern in the amorphous component. The semiquantitative analysis revealed that COPD patients have a significantly reduced expression of both EC-SOD and fibulin-5 (0.59±0.64 and 0.62±0.61, respectively) in alveolar, bronchiolar and arteriolar walls compared to control subjects (1.39±0.63 and 1.55±0.52, respectively, p<0.05). No significant changes in mRNA levels of these proteins were observed between groups. Among the oxidation markers, malondialdehyde was the best in distinguishing COPD patients.
COPD patients show a reduced expression of EC-SOD and fibulin-5 in the lung interstitium. Paralleling the reduction of EC-SOD levels, the decrease of fibulin-5 expression in COPD lungs supports the hypothesis of an impaired pulmonary antioxidant response in COPD patients.
本研究旨在分析慢性阻塞性肺疾病（COPD）患者和对照组肺部主要抗氧化剂超氧化物歧化酶（细胞外超氧化物歧化酶，EC-SOD）及其主要结合蛋白纤连蛋白-5的表达情况，以及几种氧化和亚硝化衍生产物的表达情况。
分析了19例COPD患者和20例对照者的肺组织样本。通过光镜和电镜组织化学技术评估弹性纤维的结构，采用免疫组织化学和逆转录聚合酶链反应（RT-PCR）分析EC-SOD和纤连蛋白-5的水平。通过对4-羟基壬烯醛（4-HNE）、丙二醛（MDA）和3-硝基酪氨酸（3-NYT）加合物进行免疫定位，评估氧化应激对细胞外基质的影响。
COPD患者的肺泡壁出现弹性纤维塌陷异常聚集，在无定形成分中呈现穿孔模式。半定量分析显示，与对照组相比，COPD患者肺泡、细支气管和小动脉壁中EC-SOD和纤连蛋白-5的表达均显著降低（分别为0.59±0.64和0.62±0.61），而对照组分别为1.39±0.63和1.55±0.52，p<0.05。两组间这些蛋白的mRNA水平无显著变化。在氧化标志物中，丙二醛在区分COPD患者方面表现最佳。
COPD患者肺间质中EC-SOD和纤连蛋白-5的表达降低。与EC-SOD水平降低相平行，COPD肺组织中纤连蛋白-5表达的减少支持了COPD患者肺抗氧化反应受损的假说。
