Protective effects of ulinastatin on ischemia-reperfusion iiyury during rat non-heart beating donor lung transplantation

Objective To investigate the protective effects of ulinastatin (UTI) on ischemiareperfusion injury of donor lungs,and the possible mechanism.Method Forty male SD rats were randomly divided into two groups:group C as control group and group U as UTI group.In group C donor lungs were antegradely flushed with 20 ml of cold (4 C) low potassium dextron (LPD) solution and 5 ml retrogradely.Meanwhile,in group U,UTI (500 000 U/L) was added in LPD solution and the same doses were used.According to the time after initiation of reperfusion,each group was divided into two subgroups:30 min (subgroup A) and 1 h (subgroup B).Arterial blood samples were collected for blood gas analysis.Lung samples were obtained at the end of reperfusion (30 min or 1 h).Microscopic examination of the donor lungs was conducted.Besides,the pulmonary water index (W/D),tissue malondialdehyde (MDA) and superoxide dismutase (SOD) content,and mRNA expression of tumor necrosis factor (TNF-a),intercellular adhesion molecule 1 (ICAM-1) and interleukin 10 (IL-10) were also measured.Results (1) One h after reperfusion,oxygenation index in group U was higher than that in group C (P =0.025) ; (2) The levels of W/D in subgroup A and subgroup B of group U were decreased as compared with group C (P =0.005 and P =0.006) ; (3)The microscopic changes of donor lung tissues in group U were lessen than in group C; (4) In subgroup A of group U,MDA content was decreased (P=0.039),and SOD content was increased (P=0.035),and similar results could be observed in subgroup B of group U (P =0.006 and P =0.030 respectively); (5) As compared with group C,the mRNA expression of TNF-α in group U was decreased at the time of 30 min after reperfusion (P =0.000),but no significant change was found at the time of 1 h (P =0.139).The mRNA expression of ICAM-1 was not decreased evidently at the time of 30 min (P=0.062),but significantly decreased at the time of 1 h (P=0.001).The mRNA expression of IL-10 was increased in subgroups A and B (P =0.004 and P =0.000 respectively).Conclusion This study demonstrated that UTI had protective effects of reducing ischemia-reperfusion injury on the donor lungs after lung transplantation in rat non-heart beating donor models. Key words: Lung transplantation;  Non-heart beating donor;  Reperfusion injury;  Ulinastatin