Apoptosis And Its Role In The Chronic Obstructive Pulmonary Disease

Chronic Obstructive Pulmonary Disease (COPD) is a major cause of chronic morbidity and mortality throughout the world.COPD is characterized by chronic inflammation throughout the airways, parenchyma, and pulmonary vasculature. In addition to inflammation, two other processes thought to be important in the pathogenesis of COPD are an imbalance of proteinases and antiproteinases in the lung, and oxidative stress.They are the most prevailing hypothesises for the pathogenesis of COPD.However,they does not fully explain the mechanisms behind the eradication of septal structure and the unique nature of lung destruction as compared with alterations seen in other inflammatory lung diseases.An alternative hypothesis,apoptosis, presently being investigated posits the loss of alveolar wall wall structures.It is insufficient of the study of apoptosis and COPD. For example ,no much attention has been paid to the study of the apoptosis of the neutrophils and alveolar macrophages(AM) in COPD, which might play an important role in the pathogenesis of chronic airway inflammation. Second, what are the differences in apoptosis of the lung tissue among different classification of COPD by severity? Third, what is the difference in apoptosis between COPD patients and animal model? Answers to these problems above are of theoretical significance and potential clinic value by providing information on role of apoptosis in COPD and novel therapeutic way to prevent early destruction of lung tissue.MethodBased on the information available,the model of COPD in rats were replicated by smoking. Using the techniques of HE(Hemotoxin and Eosin), immunohistochemistry, In situ hybridization and TdT mediated nick end labeling(TUNEL),we had explored the role of apoptosis ,cell proliferation, expression of apoptosis-regulating genes, and the protective effect of dexamethmasone(DEX) in the rats COPD model. We also examined the percentage of positive cells and distribution of apoptosis cell, proliferating cells in lung tissue of COPD patients with different classification severity. The dynamics changes of apoptotic polymorphoneuclear(PMN) and AM in COPD patients were measured by flow cytometry and TUNEL techniques.Results1. Chronic airway inflammation were seen in wistar rats after smoking for 1 month. In rats, 2 months after smoking ,we found the enlargement of airspaces distal to the terminal bronchiole, the destruction of alveolar walls, and loss of the alveolar unit.The number of inflammatory cells was lower in DEX group than 2 model groups.2. Both apoptotic cells and proliferative cells were found in the lungs of 4 groups rats. The rate of apoptosis (apoptosis index ,AI) and PCNA index(PI)were significantly higher in lungs of 2 model groups as compared with control group. The AI in rats treated with DEX was higher than 2 model groups, especially in airway epithelium. The ratio of PI/AI in 2 model groups and DEX group in airway epithelium were much lower than normal group. After smoking for 2 months,the ratio of PI/AI in small pulmonary vessels was significantly higher than normal group and DEX group.3.The expression of apoptosis regulating-genes such as bcl-2(mRNA and its protein), caspase-3 protein were obviously up-regulated in 2 model groups and DEX group.Similar phenomena of apoptosis and proliferation were seen in the patients with COPD,cxecpted the severe group..4. Both the survival gene(bcl-2) and death promoting gene(caspase-3) were seen in lungs of patients with COPD.Bcl-2 levels were obviously higher in mild and moderate groups as compared with control group,but its levels were not much hijher in severe group. The expression of caspase-3 was up-regulated markedly in all 3 groups of COPD patients.5. Apoptotic rate of PMN in peripheral blood decreased markedly in COPD patients and acute patients were remarkably higher than those in controls and convalescent patients respectively; However, necrotic cells obviously increased in COPD patients ,In acute patients , necrotic cells increased obviously than those in control and...