Ulinastatin Protects Against Endotoxin-induced Acute Respiratory Distress Syndrome In Rabbits

Objective: ARDS models of white rabbits were reproduced with endotoxin (LPS)injection in this study. The possible mechanisms such as inflammatory reaction,oxidative stress and disorders between hemostasis and fibrinolysis were further studiedby observing changes of pathophysiology of LPS-induced ARDS models. Ulinastatin(UTI) injection protecting against endotoxin-induced lung injury was studied in rabbits.Methods: Twenty four male white rabbits were randomly assigned to three groups:control group (A), injury group (B) and therapeutic group (C). There are eight animalsin each group. ARDS model of rabbits were replicated with intravascular LPS injection(800μg/kg) at a time in group B and C, and meanwhile UTI (10x104U/kg) wasintravascularly injected as therapeutic measure in group C. Group A were used ascontrast group injected with same saline. During the experimental course, arterial bloodpressure, arterial blood gases, SOD, MDA, IL-6, IL-8, t-PA and PAI-1were measuredat0h,0.5h,2h and4h respectively. Lung homogenate SOD and MDA were alsodetected. After rabbits were killed, the wet-to-dry lung weigh ratio was measured andpathological changes of lung tissue were observed by light microscope.Results:1. Breathing rate (R), heart rate (HR) and blood pressure (BP): R, HR of group Bsignificantly increased, BP decreased significantly (p<0.01); R, HR of Group Cslightly accelerate, BP declined slightly.2. Blood gas analysis: PaO2and OI in group B were significantly lower than in group A（p<0.01）; PaO2and OI in group C decreased significantly（p<0.01）, which was lessthan that in group B.3. Bronchoalveolar lavage: Protein content, cell count, neutrophil count, lymphocytecount, IL-6, IL-8and TNF-α levels of bronchoalveolar lavage fluid (BALF) in group B compared to group A were significantly higher (p<0.05); which were significantlylower than group B (p<0.05).4. IL-6, IL-8levels in serum: Serum IL-6, IL-8level were significantly increased ingroup B(p<0.01); IL-6, IL-8levels in group C also tended to increase, but the resultwere lower than those in group B(p <0.05).5. Plasma t-PA, PAI-1content: Plasma t-PA and PAI-1were significantly increased afterexperment in group B(p<0.05); Plasma t-PA and PAI-1contents in group C alsotended to increasing, but they were lower than those in group B(p<0.05).6. The wet-to-dry lung weight ratio IL-6, IL-8, t-PA, PAI-1, SOD activity and MDAcontent in lung tissue were higher in group B than those in group A and groupC(p<0.01).7. The presence of pathology: The structure of lung tissue in group A is normol. Thestructures of lung tissue in group B were significantly injured, such as alveolaredema, inflammatory cell infiltration, blood stasis, microvascular thrombosis, andwhite blood cells attached to the wall, thickeness of alveolar wall and wideness ofalveolar septum widen. The injured degrees of lung tissue in group C were slighterthan those in group B.Conclusion:1.ARDS model of New Zealand white rabbits can be reproduced by a singleinjection of LPS (800μg/kg).2.Pro-inflammatory and anti-inflammatory imbalance, oxidative damage andanti-oxidation imbalance, imbalance of coagulation and fibrinolysis may be theimportant factors both in taking place and development of ARDS.3.UTI may have something to do with the protective effects of ARDS byantagonizing inflammation, improving antioxidant capacity and balancingcoagulation and fibrinolysis.