Apoptosis And Proliferation Of Pulmonary Cells In Rats With COPD Induced By Smoking

Objective: To observe the changes of apoptosis and proliferation of pulmonary cells in rats with chronic obstructive pulmonary disease (COPD) induced by smoking.Methods: Twenty-four male Sprague-Dawley rats were randomly divided into a normal control group (N group) and a smoking exposure group (S group). Rat model of COPD was established by exposure to cigarette smoke for 80 days. Then S group rats were randomly subdivided into two subgroups: S₁ and S₂ subgroups, N group rats were randomly subdivided into two subgroups: N₁ and N₂ subgroups. Pulmonary function was detected in S₁ and N₁ subgroups; the mean pulmonary arterial pressure was detected by right-heart catheterization in S₂ and N₂ subgroups. The counts of total leukocytes, the percentages and counts of macrophages and neutrophils in bronchoalveolar lavage fluid were examined. Lung tissue sections stained by HE were observed to study the morphological alternations and mean linear intercept and mean alveolar numbers were measured. Paraffin-embedded lung tissue sections were evaluated for apoptosis and proliferation using terminal deoxynucleotide transferase-mediated dUTP nick-end labeling (TUNEL) or immunohistochemistry for proliferation cell nuclear antigen (PCNA). The right ventricular hypertrophy index was measured. T test, sepnce approximate t-test and Pearson correlation were conducted in SPSS 13.0.Results:1. There was no statistical difference between weights in N [(204.67±16.83)g,(257.00±23.64)g] and S group [(208.42±10.27) g,(253.45±28.24) g] before experiment and after 30 days (P＞0.05), however there was statistical difference in two groups after 80 days [(380.63±42.24) g, (299.51±30.11) g, P＜0.05].2. There were inflammatory cells infiltrations in the lung tissue and destruction of alveolar walls and enlargement of alveolar space in rats after 80 days. The counts of total leukocytes, the percentages and counts of macrophages and neutrophils in BALF were significantly increased in S group compared with those in N group (all P＜0.05) and MLI was significantly higher in S group than in N group (P＜0.05) while MAN was decreased on the contrary (P＜0.05).3. Pulmonary function test showed that FEV_0.3, FEV_0.3/FVC and PEF were lower in S₁ subgroup than in N₁ subgroup (all P＜0.05).4. The apoptotic index (AI) of bronchial epithelial cells, alveolar epithelial cells, pulmonary artery endothelial cells (PAEC) and pulmonary artery smooth muscle cells (PASMC) were (14.00±1.01)%, (9.99±1.00)%, (4.10±0.42)%, (4.16±0.48)% respectively in S group, the differences being significant (all P＜0.05), as compared with N group [(2.28±0.50)%, (2.07±0.43)%, (0.19±0.05)%, (0.20±0.05)% respectively].5. The proliferation index (PI) of bronchial epithelial cells, alveolar epithelial cells, PAEC and PASMC were (12.08±0.59)%, (8.02±0.21)%, (3.72±0.25)%, (5.71±0.44)% respectively in S group, the differences being significant (all P＜0.05), as compared with N group [(1.41±0.11)%, (1.46±0.09)%, 0.00%, 0.00% respectively].6. The ratio of PI/AI of bronchial epithelial cells, PAEC and PASMC were (86.64±8.21)%, (91.64±10.77)%, (138.91±18.38)% respectively in S group, the differences being significant (all P＜0.05), as compared with N group [(64.92±20.20) %, 0.00%, 0.00% respectively]. There was no statistical difference between the ratio of PI/AI of alveolar epithelial cells in S and N group (P＞0.05).7. MLI of lung tissue showed a positive correlation with the AI of alveolar epithelial ceils (r＝0.66, P＜0.05) while MAN a negative correlation with the latter (r＝-0.77, P＜0.05).8. The mPAP in S₂ subgroup was significantly higher than that in N₂ subgroup (P＜0.05), however there was no statistical difference between RVHI in N and S group (P＞0.05).Conclusions:1. Rat model of COPD can be successfully established by exposure to smoking.2. There are abnormal apoptosis and proliferation in pulmonary cells of rats with COPD induced by smoking.3. These results suggest that the abnormal changes of apoptosis and proliferation of pulmonary tissue in COPD rats may partly prompt the development of COPD.