The Experiment Studies Of Protective Effects Of Caspase-3 Inhibitor On Lung Ischemia-reperfusion Injury

Objective: To investigate the affects about apoptosis and related protein of caspase-3 inhibitor on lung ischemia-reperfusion injury, to study of protective effects of caspase-3 inhibitor and protect lung from IR injury.It might provide us the basis about lung transplantation Protection.Methods:We established rabbits model of pulmonary LIR in vitro. 32 rabbits were randomly divided into two groups:as contrast group and trail group.each group has eight rabbits.In cntrast group,the harversted lung blocks were flushed with and stored in the modified Low potassium dextrane (LPD) solution at 4℃for 6 hour (LPDs+6h). In trail group, harversted lung blocks were flushed with and stored in the modified Low potassium dextrane (LPD) solution containing caspase-3 inhibitor (Z-DEVD-FMK to 25umol/L) at 4℃for 6 hour (LPDs+6h+caspase-3 inhibitor Z-DEVD-FMK). After 2 hours reperfusion , the transplanted lung excised and samples were taken for H-E stain ,TUNEL, electron microscopy and the wet/dry ratio. caspase-3 protein expression were excised.Results:(1)Compared with the contrast group, caspase-3 inhibitor Z-DEVD-FMK treatment group showed decreased wet/dry ratio from 6.15±0.37 to 5.31±0.23 (p<0.05) , pulmonary edema is to ease.(2)Pulmonary H-E stain showed edema(both interstitial and a lveolar space) and neutrophil infiltration in alveolar tissue and damage of alveolus after 2h of reperfusion. The trail group is to ease. (3)With TUNEL detection apoptotic index was decreased from 9.96±2.49 to 6.27±2.35 (p<0.05). Total apoptotic cell was prominent decreased. (4)With caspase-3 protein average optical density detection index was decreased from 0.216±0.031 to 0.109±0.026 (p<0.05). (5)In contrast group ,electron microscope showed swollen vascular endothelial cells, tumid mitochondria, less microvilli on the surface of alveolar type II cells, loose or emptied lamellar bodies, condensed cytoplasm and nuclear chromatin etc.Compared with contrast group, caspase-3 inhibitor Z-DEVD-FMK treatment group showed mitigated.Conclusion: (1)Pulmonary edema, formation with neutrophil infiltration indicate that injury of lung tissue after ischernia and reperfusion. The apoptosis involved in the lung ischaemia-reperfusion injury.Most apoptotic cells are alveolar type II cells. (2)Caspase-3 inhibitor can inhibit lung apoptosis by inhibiting caspase-3 protein expression. It has protective effect in the LIRI.