[Dynamic change of apoptosis of alveolar cells in ischemia-reperfusion induced pulmonary injury: an experimental study with rats].

OBJECTIVE

To observe the dynamic changes of alveolar apoptosis in ischemia-reperfusion (IR) induced pulmonary injury, and to evaluate the roles of these two cell death styles, apoptosis and necrosis, in the progress of lung function deterioration in pulmonary IR injury.

METHODS

Fifty-four Sprague-Dawley rats were made ischemia/reperfusion models by ischemia and reperfusion in situ in single lung. Thirty-six of the 54 rats in the experimental group were re-divided into 6 equal subgroups to undergo detection of partial pressure of oxygen (PaO2) of blood in left atrium, detection of lung tissue wet weight/dry weight ratio, histology of lung by light microscope, examination of ultrastructural changes of cells by transmission electron microscopy, and quantitative detection of apoptotic cells in the right middle lobe by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) 0 h, 0.5 h, 1 h, 2 h, 6 h, and 12 h respectively after the reperfusion (subgroups R0, R(0.5), R1, R2, R6, and R12). Another 18 rats in the experimental group were re-divided into 3 subgroups of 6 rats to undergo insertion of venous catheter into the main pulmonary artery via right ventricle to perfuse trypan blue so as to evaluate the cell death degree. The death index was observed under light microscope and the necrosis index was indirectly calculated by the equation: death index = apoptotic index + necrosis index. Thirty-six rats underwent sham operation. Twelve rats were used as preoperative blank controls.

RESULTS

Proliferation of alveolar type II, but not alveolar type I cell, accompanied by ultrastructural morphological changes were seen 1 h, 2 h, and 6 h after reperfusion, the most prominently 2 h after reperfusion. Apoptotic index was elevated since 1 h after reperfusion, and peaked 2 h after reperfusion. Statistical analysis indicated that, compared with apoptotic index, the necrotic index was of more prominent correlation with blood oxygen partial pressure and wet/dry weight ratio.

CONCLUSION

Alveolar apoptosis occurs in the early stage of reperfusion, and becomes the most prominent 2 h after reperfusion. Most apoptotic cells are alveolar type II cells. In the two styles of cell death in pulmonary IR injury, alveolar necrosis is more prominently correlated with progress of lung function deterioration.