The Protective Effects Of Sildenafil On The Lung Ischemia Reperfusion Injury Under The Orthotopic Autograft Rabbits Lung Transplantation Model

Objective:Using the orthotopic autograft lung transplantation model to investigate the protective effects of sildenafil on lung ischemia reperfusion injury of rabbits,and explore the possible mechanism.Method:20 adult rabbits,each Weigh 2.5-3.0Kg(Provided by the animal experiments center of the Faculty of Medicine of Jiangsu University),were divided into two groups(CONTROL group and Sildenafil group)randomly,10 in each group.To establish the orthotopic autograft lung transplantation model,In CONTROL group,the lungs were perfused and preserved with LPD solution,the others were with LPD+Sildenafil solution which added Sildenafil 0.7mg/L into LPD solution.Before ischemia,1h and 2h after reperfusion,P_VO₂ ananysis of blood from left inferior pulmonary vein;Before ischemia,0.5h,1h,1.5h and 2h after reperfusion SOD activity,iNOS activity ananysis of blood from left inferior pulmonary vein;2h after reperfusion MDA level and MPO activity from lungs tissue were run;At the end of the operation got the lung tissue for lung wet/dry weight ratio and examined for pathology.Results:1.The comparison of the partial pulmonary vein oxygen pressure after the reperfusion:The P_vO₂ all decreased after reperfusion in two groups,but it was higher in Sildenafil group than that in CONTROL group at the same time.It was significant(P＜0.05).2.MDA level,SOD activity:The MDA level was lower in Sildenafil group than that in CONTROL group after reperfusion;The SOD activity all decreased after reperfusion in two groups,but it was higher in Sildenafil group than that in CONTROL group in the same time.The results of two groups has significance(P＜0.05) after reperfusion..3.MPO,i NOS activity:The MPO activity was lower in Sildenafil group than that in CONTROL group;The iNOS activity all increased after reperfusion in two groups,but it was lower in Sildenafil group than that in CONTROL group in the same time;.The comparison of MPO,i NOS activity in CONTROL group and Sildenafil group has significance (P＜0.05) after reperfusion.4.W/D of lung tissue:the comparison of the lung tissue W/D in CONTROL group and Sildenafil group shows significance(P＜0.05).5.The pathological changes in lung tissue through optical microscope: in SILDENAFIL group,Lung tissue cell wall is slightly widened,the vascular endothelial is integrity,there are blood-cells in the vessel;But in the control group,pulmonary alveolar wall is widened,accompanied by scattered in the fibrin deposition,vascular endothelial is also integrity,a large number of neutrophils infiltrated,it can be seen a number of alveolar phagocytic cells,accompanied by the neutrophil aggregation. 6.The pathological changes in lung tissue through electron microscope: in SILDENAFIL group,most of the alveolar organizational structure is normal,typeâ… and typeâ…¡alveolar epithelial cells are generally normal, part of alveolar epithelial cells edemaed and fell off.The surface villi is still visible,lamellar body is particularly prevalent,alveolar lumen is basically patent.However,RBC can be seen in a small number of alveolar cavities.In some regional,capillary is filled with erythrocyte,a few inflammatory cells infiltrated can be seen;but in the CONTROL group,the capillary in the alveolar septa is hyperaemic obviously,the blood vessel is dilatated,the RBC leakage in alveolar cavity is obvious, deposited in piles,accompanied by the exudation of cellulose,infiltration of neutrophils can be seen,accompanied by a few of monocaryotic cells. Some of the alveolar epithelium cells edemaed and fell off to result alveolar wall became thinner or broken,some of alveolar epithelial cells aqtocytolysis.The lamellar bodyin typeâ… and typeâ…¡alveolar epithelial cell cytoplasm was emptied.Conclusion:In the orthotopic autograft lung transplantation model of rabbit,Sildenafil can eliminate oxygen free radicals with its strong anti-oxidation mechanism and can attenuates inflammation reaction with its anti-inflammation mechanism,resulting in alleviating lung reperfusion injury of pulmonary grafts,and improve the early pulmonary function after the transplantation.The Sildenafil maybe useful for lung preservation in the orthotopic autograft lung transplantation model in rabbit.