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. 2022 Jun;58(6):482-489. doi: 10.1016/j.arbres.2020.12.032. Epub 2021 Jan 27.
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 COPD 患者和对照组肺组织中主要抗氧化剂超氧化物歧化酶（EC-SOD）、其主要结合蛋白 Fibulin-5 以及几种氧化和硝化衍生产物的表达。
分析了 19 名 COPD 患者和 20 名对照者的肺组织样本。采用光镜和电镜组织化学技术评估弹性纤维结构，采用免疫组化和 RT-PCR 分析 EC-SOD 和 Fibulin-5 的水平。通过 4-羟壬烯醛（4-HNE）、丙二醛（MDA）和 3-硝基酪氨酸（3-NYT）加合物的免疫定位，评估氧化应激对细胞外基质的影响。
COPD 患者的肺泡壁显示出异常堆积的塌陷弹性纤维，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 患者的肺泡、细支气管和小动脉壁中 EC-SOD 和 Fibulin-5 的表达显著降低（分别为 0.59±0.64 和 0.62±0.61）（分别为 1.39±0.63 和 1.55±0.52，p<0.05）。两组间这些蛋白的 mRNA 水平无明显变化。在氧化标志物中，丙二醛在区分 COPD 患者方面表现最佳。
COPD 患者的肺间质中 EC-SOD 和 Fibulin-5 的表达降低。与 EC-SOD 水平降低相平行，COPD 肺中 Fibulin-5 表达的减少支持 COPD 患者肺抗氧化反应受损的假说。
