Von Willebrand Factor And Vascular Endothelial Growth Factor In Oleic Acid-Induced Acute Lung Injury In Rabbits

Objective:Vascular endothelial injury and dysfunction are the important pathological feature in the early stage of acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). Acute lung injury model of rabbits induced by oleic acid was used to observe the changes in the level of von Willebrand factor (vWF) and vascular endothelial growth factor (VEGF) in samples of blood, and the effect of low tidal volume and high positive end expiratory press ventilation strategy on them. To investigate the expression of vascular endothelial injury in ALI/ARDS and the biological mechanism of low tidal volume and high positive mechanical ventilation strategy in therapy of ALI/ARDS, the experiment was performed.Methods:The experiment was carried out in Ultrasound Institute of ChongQing Medical University and levels of vwF and VEGF were examined in Basic Research Laboratories of ChongQing Medical University. Thirty healthy New Zealand white male rabbits weighting between 3.2 and 3.8kg were randomly divided into 3 groups with 10 in each group.⑴Normal control (NC) group: injected with 0.1ml/kg saline via venous;⑵Oleic acid (OA) group: injected with 0.1ml/kg oleic acid via venous;⑶Oleic acid + low tide volume (VT) + high positive end-expiratory pressure (PEEP) ventilation (OA+LVHP) group: supine position, after 12h of oleic acid injection the rabbits were ventilated with VT 5ml/kg, PEEP 10mH2O, 100% oxygen, I:E 1:2, R: 30times/min. Blood samples were gotten at 2h, 4h, 8h, 12h in each group and the levels of vWF and VEGF were observed by ELISA. At the same time, blood gas analysis was taken to monitor the arterial oxygen partial pressure (PO2). After 12h of oleic acid injection, these animals were killed and their lungs were taken out to measure their wet weight (WW), dry weight (DW) and lung wet-to-dry weight ratio (W/D). Lung tissues pathology was observed under light microscope.Results:Thirty rabbits were involved in the analysis of results finally.⑴PO2 significantly decreased in OA group compared with NC group (p<0.05). From 4h to 12h of OA+LVHP group, PO2 significantly increased compared with OA group (p<0.05).⑵The level of vWF in serum significantly increased in OA group compared with NC group (p<0.05). Their levels had no great differences between OA+LVHP group and OA group (p>0.05).⑶The level of VEGF in serum significantly increased in OA group compared with NC group(p<0.05). Their levels had no great differences between OA+LVHP group and OA group (p>0.05).⑷WW and the ratio of W/D significantly increased in OA group compared with NC group (p<0.05). WW and the ratio of W/D significantly decreased in OA+LVHP group compared with OA group (p<0.05).⑸The lung volume increased markedly in OA group and the lungs became dark red with a little bit bleeding lesions. The extent of pulmonary edema was decreased markedly in OA+LVHP group compared with OA group, and most parts of the lungs in OA+LVHP group became pink, a few parts are dark red with a small amount of bleeding points. OA group was characterized by a wider alveolar septum, a large number of neutrophil infiltration, alveolar wall swelling and destruction, a large number exudation and hemorrhage and micro-vascular thrombosis. Alveolar septum slightly widened and a small amount of neutrophil infiltration, a small amount of exudation and hemorrhage were seen in OA group.Conclusion:⑴The levels of vWF and VEGF were increasing with the extent of lung injury in the early stage of ALI induced by oleic acid, and their levels may be considered the main indicators for the early ALI.⑵Low tidal volume and high PEEP ventilation can ease the extent of pulmonary edema, but had no effects on vWF and VEGF in blood.