| BACKGROUND:1. Ischemia-reperfusion(IR) injury in lung occurs in various clinical practice, and is considered one important reason for pulmonary dysfunction in early stage after lung transplantation and cardiopulmonary bypass. Cell apoptosis was found in IR of many organs such as liver,heart,nervous system, renal and retina, and was regarded a signal of IR deterioration and poor outcome. Little is known on alveolar apoptosis during lung IR, and the apoptotic cell types , the dynamic progress of apoptosis in lung IR, as well as the correlation between apoptosis and pulmonary dysfunction are uncertain.2. Mucosolvan (main component is ambroxol), can improve syntheses and release of pulmonary surfactant, is a clinical respiratory mucolysate. Later research revealed that mucosolvan is able to inhibit neutrophile activation, degranulation, uptake of calcium ion and release of inflammatory factors, while pulmonary surfactant depletion, neutrophile activation, calcium overload and inflammatory factors are involved in mechanisms of lung IR, and may induce apoptosis in IR. Thus, we hypothesized that mucosolvan might protect lung from IR injury, and inhibit apptosis. To our knowledge, nearly no such research has been reported.AIM:To observe the dynamic changes of alveolar apoptosis in ischemia-reperfusion (IR) induced pulmonary injury, to evaluate the contributes of the two cell death styles, apoptosis and necrosis, to the progress of lung function deterioration in pulmonary IR injury; And to observe whether mucosolvan can ameliorate pulmonary IR injury and alveolar apoptosis, and whether mucosolvan can influence the expression of bcl-2 in lung, which may be an important role of the protection by ambroxol.METHODS:1. Rats were divided into four groups randomlyGroup A: Control group(n=12), species were taken directly after anesthesia and thoracic incision. This group served as the pre-operative controls to the other groups.Group B: Sham group (n=54) , suture was only placed in left hilus. The other operation progress and analysis of species were same to IR group.Group C: Ischemia and reperfusion group (IR group,n=54), according to reperfusion time after 60min ischemia, it is further divided into six sub-groups: R0, R0.5, R1, R2, R6,R12 stand for 0min, 50min, 1h, 2h, 6h, 12h after reperfusion.Group D: Mucosolvan treatment group(n=54), five sub-groups as group C. Mucosolvan of 200mg/dL was continuously administrated intravenously ,in the speed of 0.3ml/h, from 4h before ischemia to 6h after reperfusion or the end of experiment. The same volume of NS was administrated to the other groups in the same period of time.2. We use the rat model of warm ischemia and reperfusion in situ in single lung.3. The alveolar apoptosis index was achieved by terminal deoxynucleotidyltransferase- mediated dUTP nick end labeling( TUNEL). The total cell death was evaluated via in vivo stain by trypan blue . The expression of bcl-2 in lung tissue was accessed by quantitative immunohistochemistry. And meanwhile, PaO2, hemoglobin and wet/dry ratio of lung tissue were recorded , indicating the dynamic progress of pulmonary function deterioration in ischemia-reperfusion injury. Morphological and ultrastructural changes of lung tissue was observed by either H-E stain light microscopy or transmission electron microscopy.4. All datas were represented as Mean+Standard Deviation, mean equality was calculated via t or t' test according to the equality of variances (Levene's test). P<0.05 was considered as significance. Bi-variance correlation was evaluated by Pearson Correlation Coefflciant. All the statistical analysis was carried on via SPSS 10.0 in personal computer.RESULTS:1. Wet/Dry weigh ratio increasd after 1h of post-reperfusion and reached a peak value at 6h of post-reperfusion and began to decrease at 12h of post-reperfusion.2. Blood oxygen pressure began to decrease at 1h and reach a lowest value at 6h and began to increase at 12h of post-reperfusion.3. Pulmonary H-E stain show...
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