The Study On The Effect And Mechenisms Of Endothelin Receptor Antagonist PD142893 Preconditioning On Allograft Ischemia/reperfusion Injury In Rat Lung Transplantation

Part One: The establishment of rat orthotopic lung transplantation model using cuffsObjective To establish more simple and effective rat orthotopic lung transplantation model. Method 40 male rats were randomly divided into donor and recipient groups. Rat lung transplantation model were established by using improved cuff technique. Results All operations were accomplished successfully. The mean operative time of recipient was (45±4)min. All rats survived over 30 days after lung transplantation. There was no significant difference in the blood gas analysis and chest X-ray examination (P < 0.05) before and after clipping the right hilum. Conclusion This method is more simple,applicable and requires less time. We may use it in establishing rat lung transplantation model. The expression of ICAM-1 in the allografts of rat lung transplantation after reperfusion and the effect and mechenisms of endothelin receptor antagonist PD142893 preconditioning on allograft ischemia/reperfu-sion injuryObjective To investigate the expression of ICAM-1 in the transplanted rat lungs in 24 hours after reperfusion and the effect of an ETA and ETB nonselective endothelin receptor antagonist, PD142893, on the recipient administrated before reperfusion. Method 150 male SD rats were randomly divided into three groups: (1) The endothelin receptor antagonist was administrated (I.V) before reperfusion (ETRA group, 60 rats, 30 transplantation); (2) 0.9% sodium chloride solution was administrated (I.V) before reperfusion (NS group, 60 rats, 30 transplantation). (3) The animals only received anesthesia, thoracotomy and isolation of pulmonary hilum except donor lung (SO group, 30 rats, sham operation). Blood samples from left pulmonary vein and left lung tissue samples were obtained 0h, 1h, 2h, 6h, 12h and 24h after reperfusion (ETRA group and NS group) or operation (SO group). Wet-to-dry lung weight ratio and MPO activioty of lung samples were measured. The PaO2 of blood samples was measured by blood-gas-analysis. The protein and mRNA expression of ICAM-1 in left lung samples were measured by frozen immunohistochemistry and RT-PCR respectively. Results Compared with SO group, the protein and mRNA expression of ICAM-1 in ETRA group and NS group were significantly increased after reperfusion (P<0.05), with the highest expression at 6h after reperfusion. Compared with NS and SO group, the protein and mRNA expression of ICAM-1 in ETRA group, PaO2, wet-to-dry lung weight ratio and MPO activity were significantly ameliorated (P<0.05). Conclusion The data of this study indicate that the protein and mRNA expression of ICAM-1 in transplanted rate lungs were up-regulated after reperfusion, the Part Two: highest expression of which occurred at 6h after reperfusion. The ETA and ETB nonselective endothelin receptor antagonist PD142893 could ameliorate the ischemia-reperfusion injury of transplanted lungs and improve the transplanted lung function. In this study we can suppose that reducing the expression level of ICAM-1 in the allograft and the following recruiting of neutrophils in the transplanted lungs were probably the important mechanisms of PD142893 in allograft.