Ulinastatin,a Human Protease Inhibitor,Attenuates Ischemia-reperfusion Lung Injury

Purpose To study the mechanism of lung ischemia-reperfusion injury and the protective effects of ulinastatin on lung ischemia-reperfusion injury. Methods Sixty healthy Sprague-Dawley rats were randomly divided into three groups:C group,U group and IR group.Five rats were put to death at one of four time points(45 min ischamia 30,60 and 120 min reperfusion) in each group after blood was collected from the left carotid and them discarded the left lung.The TNF?α concentration in plasma,the dry/wet(D/W) ratio and the contents of superoxide dismutase(SOD) in lung tissue were determined and lung biopsies were also obtained. Results (1) The TNF?α concentration in plasma:In IR group TNF?α was increased obviously at the 30 min,60 min,and 120 min reperfusion and it was significantly higher than that in the C group and U group(P0.05).The increase of TNF?α was meaningless in the U group.(2) The contents of SOD in lung tissue:SOD in both the IR group and U group were significantly lower in each same time point after ischemia-reperfusion than that in the C group(P0.05),but the decreased level of SOD in the U group was obviously less than that in the IR group(P0.05).(3) The D/W ratio of lung tissue:After ischemia-reperfusion,the D/W in the IR group and U group were decreasing progressively and reached the lowest at 120 min after reperfusing(60,120 min reperfusion vs 45 min ischemia,P0.01);the degree for D/W decreasing in the U group was obviously less than that in the IR group(at 60,120 min reperfusion,the U group vs the IR group,P0.05).(4) Histological evaluation:In the process of ischemia-reperfusion the lung injury was aggravating progressively in the IR group;there was marked pulmonary capillary congestion,interstital edema and intraalveolar hemorrhage,infiltration;the electron microscopic section of alveolar showed the type Ⅱ pneumocyte was damaged and lamellar bodies disappeared.The pulmonary pathologic alterations occurred to a lesser degree in the U group compared with the IR group. Conclusions (1) The lung ischemia-reperfusion injury may have close relationship with cytokinin released increasingly and unbalancingly between free radicals generating and clearing;(2) Ulinastatin,a protease inhibitor,could decrease cytokinin releasing,inhibit neutrophils aggregating and activated in the lungs and increase free radicals scavenging.It could be used to protect lung ischemia-reperfusion injury.