Protective effect of ulinastatin on lung injury in rats with moderate burn-blast combined injury

Abstract

Objective To investigate the protective effects of ulinastatin on lung tissue in rats following moderate burn-blast combined injury and its mechanism. Methods One hundred and twenty male Sprague-Dawley rats were randomly divided into four groups: sham+ saline group (group SS, n=20), sham+ ulinastatin (group SU, n=20), burn-blast combined injury+ saline(group BBS, n=40) and burn-blast combined injury+ ulinastatin (group BBU, n=40). Rats in the group BBS and BBU were subjected to a model with moderate burn-blast combined injury. Rats in the group SS and SU were anesthetized, in addition to no hurt, other interventions the same to the model with moderate burn-blast combined injury. Immediately after injury rats were intravenously given either 1 mL saline in group SS and BBS or 1 mL saline containing ulinastatin(40000 U/kg) in group SU and BBU. The rats were sacrificed at the end of experiment and observed the pathological changes of lung tissue in rates by optical microscope. Lung tissues were harvested for the measurement of acetylated histone H3 by Western Blot and heat shock protein 70 by enzyme-linked immuno sorbent assay. The rates of tissue water content in lung were determined by the dry/wet weight. Results At 6 h after injury, the lung injury score of group BBU and group BBS were (5.82±0.37) points, (4.20±0.32) points, the expression of heat shock protein 70 in group BBU and group BBS were (205.0±2.3) pg/mL, (220.0±2.4) pg/mL, the expression of acetylation histone H3 Lys9 in group BBU and group BBS were 0.68±0.13, 1.45±0.12, the water content of lung tissue in group BBS and group BBU were (85.30±2.13)%, (82.80±1.57)% respectively. At 24 h after injury, the lung injury score of group BBU and group BBS were (8.25±0.42), (6.11±0.31) points, the expression of heat shock protein 70 in group BBU and group BBS were (221.0±2.4) pg/mL, (226.0±2.7) pg/mL, the expression of acetylation histone H3 Lys9 in group BBU and group BBS were 1.59±0.17, 1.78±0.15, the water content of lung tissue in group BBS and group BBU were (85.80±1.57)%, (80.20±0.32)% respectively. The lung injury scores of group BBS and group BBU were significantly different at 6 h and 24 h after injury (t=6.132, 6.791, P=0.026, 0.016), the water content of lung tissue in group BBS and group BBU were significantly different at 6 h and 24 h after injury (t=6.123, 5.894, P=0.034, 0.019), the difference of the expression of heat shock protein 70 and acetylation histone H3 Lys9 at 6 h after injury between group BBS and group BBU was statistically significant (t=2.795, 3.165, P=0.031, 0.028), while the expression of heat shock protein 70 and acetylation histone H3 Lys9 had no significant difference at 24 h after injury (t=2.143, 3.154, all P values were greater than 0.05). At 6 h and 24 h after injury, the lung injury scores, the water content of lung tissue, the expression of heat shock protein 70 and acetylation histone H3 Lys9 of the group BBS and group BBU had significant difference at the same time point compared with group SS and group SU (all P values were less than 0.05). Conclusions The results indicated that ulinastatin significantly alleviated burn-blast combined injury-induced lung edema and pathologic changes. These protective effects may be due to high expressions of protective proteins and increased tolerance to burn-blast combined injury. Key words: Burns; Lung injury; HSP70 heat-shock proteins; Acetylation of histone H3 lysine 9; Ulinastatin; Burn-blast combined injury