| Objective Chronic obstructive pulmonary disease (COPD), a common preventable and treatable disease, is characterized by persistent airflow limitation that is associated with an enhanced chronic inflammatory response in the airways and the lung to noxious particles or gases. The imbalance of oxidant burden and antioxidant capacity has been implicated as an important contributing factor in the pathogenesis of COPD. Superoxide dismutases(SODs)are the only enzymatic system-decomposing superoxide radicals to H2O2and are hypothesized to play a significant role against oxidant stress, especially in the lung. There are three different mammalian SODs:intra-cellular copper-zinc SOD (CuZnSOD), mitochondrial manganese-SOD (MnSOD) and extracellular SOD (ECSOD). Mitochondria is a critical cell organelle both in the cellular energy metabolism and cell survival. Mitochondria are also known to be the largest source of superoxide anion radical production within cells. MnSOD is a mitochondrial enzyme known to play an essential role in the oxidant resistance of several vital organs. The aim of this study is to investigate the location and the levels of MnSOD expression in pulmonary tissues of smokers with and without COPD, and the correlation between the levels of the MnSOD expression and lung function and the smoking index.Method Lung tissue samples from63patients undergoing resection for a lung tumour were drawn from the department of thoracic surgery of the General Hospital of TianJin, China. According to smoking or no smoking and the different airflow limitation, these tissue samples were assigned into10non-smokers without COPD group,15smokers without COPD group and14smokers with COPD patients with mild airflow limitation group,16smokers with COPD patients with moderate airflow limitation group, smoker with8COPD patients with severe airflow limitation group. These specimens were obtained as far from the cancer focus (>5cm) as possible. The lung tissue pathology was observed with HE staining. Immunohistochemical staining was used to investigate the expression of MnSOD in pulmonary tissues.Results1No apparent inflammatory changes were observed in non-smokers group. Small airway and alveolar interval of smoking without COPD can be seen a slight congestion, hemorrhage and a small amount of inflammatory cell infiltration. COPD group, from mild to severe group, the lung tissue structural damage and inflammatory cell infiltration gradually increase.2When analysed from the whole material of the nonsmokers, the expression of MnSOD was intense in the central bronchial epithelium(0.998±0.145) and in the alveolar macrophages(1.451±0.166), as well as the small bronchial epithelium (0.484±0.061).Alveolar epithelial cells(0.052±0.016) is almost no expression(p<0.001). The difference being statistically significant between central bronchial epithelium and small bronchial epithelium (p<0.001), as well as between alveolar macrophages and small bronchial epithelium(p<0.001). MnSOD expression of the alveolar macrophages was higher than that of the central bronchial epithelium (p<0.001).When the nonsmokers and smokers with or without COPD were compared, the level of MnSOD expression was clearly elevated in the the central bronchial and alveolar macrophages and alveolar epithelium of smokers’lungs (p<0.001). MnSOD did not differ in the peripheral bronchiolar epithelium (p>0.05). When smokers with COPD and smokers without COPD were compared, MnSOD did not differ (p>0.05).When the level of MnSOD expression in the central bronchial epithelium alveolar macrophages and alveolar epithelium were compared between the smokers and subjects with COPD with mild-moderate, MnSOD immunoreactivity Showed an increasing trend, but the difference was not statistically significant(p>0.05). Compared to smokers without and with COPD mild-morderate, MnSOD immunoreactivity in the central bronchial epithelium and alveolar epithelium of COPD with severe airflow limitation decreased, but the difference was not statistically significant (p>0.05).3the level of MnSOD expression in the central bronchial epithelium(r=0.595) and the alveolar macrophage(r=0.508) and the alveolar epithelial cells (r=0.795) of COPD’s lung positively correlated with smoking index (p<0.001).4The level of MnSOD expression in the central bronchial epithelium (r=-0.259, p<0.05) and alveolar epithelium (r=-0.365, p<0.05)of COPD’s lung negatively correlated with FEV1%.5The level of MnSOD expression in the central bronchial epithelium(r=-0.262) and alveolar epithelium (r=-0.260) of COPD’s lung negatively correlated with BMI(p<0.05).Conclusion1HE staining reveal that from without airflow limitation to severe airflow limitation, the damage to lung tissue of smokers with and without COPD gradually increased;2When the nonsmokers and smokers with or without COPD were compared, MnSOD did not differ in the peripheral bronchiolar epithelium. That show the antioxidant capacity of the peripheral bronchiolar epithelium in oxidative stress may be weak;3The level of MnSOD expression in nonsmokers’lungs and smokers with COPD with mild-morderate seem be on the rise. That show antioxidant capacity may be a compensatory rise;4The level of MnSOD expression in the lung of COPD with severe airflow limitation decreased. That show early the MnSOD expression increased, but the level of increasing may not be enough against long-term of the oxidative stress, which may increasing damage to the lung tissue, resulting in reduced antioxidant capacity of the lung tissue.5the level of MnSOD expression in the lung of COPD positively correlated with smoking index. That show MnSOD in the lung play a protective role in oxidative stress.6The expression of MnSOD in the lung of COPD negatively correlated with the FEV1%predicted. This show oxidative stress may be one of the reasons leading to airflow limitation.7An negative correlation existed between BMI and the level of MnSOD expression in the lung of COPD. These results show that Oxidative stress may cause the nutrition depletion and low body weight of COPD. |
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