• W Liu and J K Chai.
• Burn Institute, the First Affiliated Hospital of PLA General Hospital, Beijing 100048, China.
• Zhonghua Shao Shang Za Zhi. 2018 Jan 20; 34 (1): 32-39.

AbstractObjective: To explore the influences of ulinastatin on acute lung injury and time phase changes of coagulation parameters in rats with severe burn-blast combined injuries. Methods: One hundred and ninety-two Sprague-Dawley rats were divided into pure burn-blast combined injury group, ulinastatin+ burn-blast combined injury group, and sham injury group according to the random number table, with 64 rats in each group. Two groups of rats with combined burn-blast injuries were inflicted with moderate blast injuries with the newly self-made explosive device. Then the rats were inflicted with 25% total body surface area full-thickness scald (hereinafter referred to as burn) on the back by immersing in 94 ℃ hot water for 12 s. Rats in sham injury group were sham injured on the back by immersing in 37 ℃ warm water for 12 s. Immediately after injury, rats in the three groups were intraperitoneally injected with Ringer's lactate solution (40 mL/kg), meanwhile rats in ulinastatin+ burn-blast combined injury group were intraperitoneally injected with ulinastatin (4×10(4)U/kg), once every 12 hours, until post injury hour (PIH) 72. Before injury, at PIH 3, 6, 12, 24, 48, 72, and on post injury day (PID) 7, 8 rats in each group were selected to harvest abdominal aortic blood samples to detect plasma levels of activated partial thromboplastin time (APTT), prothrombin time (PT), fibrinogen, D-dimer, antithrombin Ⅲ (AT-Ⅲ), and α2-antiplasmin (α2-AP). At PIH 24, three rats in each group which were used in detection of coagulation parameters were sacrificed to observe lung injury. At PIH 72, three rats in each group were sacrificed for histopathological observation of lung. Data were processed with analysis of variance of factorial design and least-significant difference test. Results: (1) Compared with those of rats in sham injury group, APTT of rats in pure burn-blast combined injury group significantly prolonged at PIH 72 and on PID 7 (P<0.05 or P<0.01). PT significantly prolonged at PIH 3 and 72 and significantly shortened at PIH 6 (P<0.05 or P<0.01) . Fibrinogen level significantly increased from PIH 12 to PID 7 (P<0.01). AT-Ⅲ level significantly decreased at PIH 6 and 12 (P<0.01), and α2-AP level significantly decreased at PIH 6 and significantly increased from PIH 24 to 72 (P<0.01). Compared with those of rats in pure burn-blast combined injury group, APTT of rats in ulinastatin+ burn-blast combined injury group significantly prolonged at PIH 3 and 6 (P<0.01) while PT significantly shortened at PIH 3, 12, and 72 (P<0.05 or P<0.01). Fibrinogen level significantly decreased at PIH 6 and 12 and significantly increased at PIH 72 (P<0.05 or P<0.01). AT-Ⅲ level significantly increased at PIH 3, 12, 48, and 72 (P<0.05 or P<0.01), and α2-AP level significantly decreased from PIH 12 to 72 (P<0.05 or P<0.01). D-dimer level of rats in sham injury group, pure burn-blast combined injury group, and ulinastatin+ burn-blast combined injury group were respectively (0.084±0.013), (0.115±0.015), (0.158±0.022), (0.099±0.011), (0.099±0.012), (0.089±0.011), (0.124±0.014), and (0.116±0.018) μg/mL, (0.064±0.033), (0.114±0.016), (0.135±0.009), (0.060±0.008), (0.104±0.010), (0.124±0.020), (0.180±0.036), and (0.201±0.032) μg/mL, (0.074±0.013), (0.084±0.035), (0.101±0.050), (0.091±0.046), (0.096±0.034), (0.044±0.019), (0.106±0.049), and (0.118±0.047) μg/mL. Compared with that of rats in sham injury group, D-dimer level significantly decreased at PIH 6 and 12 and significantly increased from PIH 48 to PID 7 (P<0.05 or P<0.01). Compared with that of rats in pure burn-blast combined injury group, D-dimer level of rats in ulinastatin+ burn-blast combined injury group significantly decreased at PIH 3, 48, and 72, and on PID 7 (P<0.05 or P<0.01). (2) At PIH 24, there was a large amount of light red effusion in the thoracic cavity, and both lung lobes were hyperemic and edematous with a small amount of blood clots in the left and middle lobe of rats in pure burn-blast combined injury group. There was a small amount of yellowish effusion in the thoracic cavity of rats in ulinastatin+ burn-blast combined injury group, and the degree of hyperemic and edematous of bilateral lobes was lighter compared with rats in pure burn-blast combined injury group with no clot in the left lobe. No congestion, edema, or bleeding was observed in lungs of rats in sham injury group. (3) At PIH 72, disorganized alveolar structure, collapsed alveolar cavity, edematous and thickening pulmonary interstitium, infiltration of a large amount of inflammatory cells, obvious rupture of alveolar septum, and hyaline thrombus were observed in lungs of rats in pure burn-blast combined injury group. Significantly improved alveolar structure, less collapsed alveolar cavity, improved edematous pulmonary interstitium, less infiltration of inflammatory cells, rupture of alveolar septum, and no thrombus were observed in lungs of rats in ulinastatin+ burn-blast combined injury group. The lung tissue had a well-filled alveolar cavity with no interstitial edema or infiltration of inflammatory cells and no thrombosis in lungs of rats in sham injury group. Conclusions: Ulinastatin has positive therapeutic effects on acute lung injury in rats with severe burn-blast combined injuries through its good regulating effects on coagulation and fibrinolytic disorders caused by burn-blast combined injuries.

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