Effects of ulinastatin on hemorrhagic shock and resuscitation-induced acute lung injury in rats

Objective To evaluate the effects of ulinastatin on hemorrhagic shock and resuscitation (HS/R) -induced acute lung injury in rats. Methods Fifteen SPF adult Sprague-Dawley rats, aged 2-3 months, weighing 300-400 g, were divided into 3 groups (n=5 each) using a random number table: sham operation group (group S) , HS/R group and ulinastatin group (group U) . Carotid arteries were cannulated for blood pressure monitoring and blood-letting.HS/R was induced by blood-letting and maintained for 1 h, followed by resuscitation with autologous blood transfusion and infusion of normal saline.After cannulation of carotid arteries (T0) , at 5 min after hemorrhagic shock (T1) , before resuscitation (T2) , at 5 min after the expected blood pressure was achieved following resuscitation (T3) , and at 30 min, 1.5 h and 2.5 h after resuscitation (T4-6) , arterial blood samples were collected for determination of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) concentrations (by enzyme-linked immunosorbent assay) . Arterial blood samples were collected at T0, T2 and T6 for blood gas analysis.The pH value, partial pressure of arterial carbon dioxide (PaCO2) , and base excess (BE) value were recorded, and oxygenation index (PaO2/FiO2) was calculated.Lungs were removed at T6, and pulmonary specimens were obtained for examination of pathological changes which were scored, and nucleus was extracted for determination of nuclear factor-kappa B (NF-κB) p65 expression by enzyme-linked immunosorbent assay. Results Compared with group S, the pH values, , BE values and OI were significantly decreased, and PaCO2, plasma IL-6 and TNF-α concentrations, expression of NF-κB p65 in lung tissues, and pathological scores were increased in U and HS/R groups.Compared with group HS/R, the plasma concentrations of IL-6 and TNF-α, expression of NF-κB p65 in lung tissues, and pathological scores were significantly decreased, and no significant changes were found in parameters of blood gas analysis in group U. Conclusion Although ulinastatin can alleviate HS/R-induced acute lung injury, it is insufficient to improve lung oxygenation in rats. Key words: Trypsin inhibitors; Shock, hemorrhagic; Cardiopulmonary resuscitation; Respiratory distress syndrome, adult