Objective: To investigate the relationship between apoptosis of alveolar epithelial cells and pulmonary vascular endothelial cells in chronic obstructive pulmonary disease (COPD) and the relationship between apoptosis and lung function and emphysema.
Methods: Twenty-four male Sprague-Dawley rats were randomly divided into a smoke exposure group (COPD group) and a normal control group (NC group). The rat model of COPD was established by exposure to cigarette smoke for 80 days, and lung tissues were obtained. Lung tissue samples were also collected respectively from patients with COPD (n = 13) and without COPD (n = 12). Lung sections stained by HE were observed to study the morphological alteration, and mean linear intercept (MLI) and mean alveolar numbers (MAN) were measured to estimate the extent of emphysema in rats. Quantitative analysis of apoptosis of alveolar epithelial cells and pulmonary vascular endothelial cells was undertaken by TdT-mediated dUTP nick end labeling (TUNEL). The data distributed normally were expressed as (-x) +/- s, and the independent-samples t-test was used for comparison of means. Nonparametric data were expressed as median (quartile range), and Wilcoxon rank sum test was used for comparison. Correlation between apoptosis of the two kinds of cells in patients with COPD was estimated by Spearman rank correlation coefficients, and the correlations between the specific indexes, such as FEV(1)%Pre, FEV(1)/FVC(%), residual volume/total lung capacity(%) [RV/TLC(%)], MLI, MAN, and the cell apoptosis were also investigated. Statistical difference was accepted at P < 0.05.
Results: Destruction of alveolar walls and enlargement of alveolar space were observed as pathological changes of lung tissues from patients and rats with COPD. The apoptotic index (AI) of alveolar epithelial cells and pulmonary vascular endothelial cells were (28.9 +/- 3.1)%, (13.2 +/- 2.6)% in patient COPD group; (10.0 +/- 1.0)%, (4.1 +/- 0.4)% in rat COPD group; the differences being significant (t = -23.946, -8.820, -24.273, -36.422, all P < 0.05), as compared with NC groups [(5.8 +/- 1.2)%, (5.6 +/- 1.5)%, (2.1 +/- 0.4)%, (0.2 +/- 0.1)% respectively]. In patient COPD group, the AI of alveolar epithelial cells was significantly higher than that of pulmonary vascular endothelial cells (t = -13.889, P < 0.05) and both were positively correlated with each other (r = 0.60, P < 0.05). In patient COPD group, both the apoptosis of alveolar epithelial cells and pulmonary vascular endothelial cells revealed negative correlations to FEV(1)(%)pre (r = -0.83, -0.69, all P < 0.05) and FEV(1)/FVC(%) (r = -0.95, -0.71, all P < 0.05), but positive correlations were demonstrated between them and RV/TLC(%) (r = 0.93, 0.70, all P < 0.05). In rat COPD group, MLI of lung tissue showed a positive correlation with the AI of alveolar epithelial cells (r = 0.59, P < 0.05) while MAN a negative correlation with the latter (r = -0.81, P < 0.05).
Conclusions: Abnormal apoptosis of alveolar epithelial cells and pulmonary vascular endothelial cells was present in patients and rats with COPD, which was related to the changes of lung function or pathological changes of lung tissues. The results suggest that the abnormal changes of apoptosis of pulmonary tissue in COPD may be involved in the pathogenesis of the disease.