Use320-slice CT To Analyze The Change Of Acute Lung Injury In Rabbits Induced By Paraquat And The Intervention Role Of Ulinastatin

ObjectiveThe ALI and its more severe stages of acute respiratory distress syndrome(ARDS) is an acute syndrome caused by excessive inflammatory response, which is characterized by progressive dyspnea and refractory hypoxemia induced by a variety of reasons of the lung inside or outside the body. It is the leading cause of death in critically ill patients, therefore it is very important significance to study the pathogenesis and treatment.320-slice CT is the only one which be able to achieve scan imaging of dynamic volume currently.It is a method of noninvasive functional imaging, which obtain the CTP images by dynamic scanning the particular level via intravenous infusion of contrast agent. Getting perfusion parameters rBF/rBV/rPS through computer processing can be used to reflect the organization hemodynamic changes in the capillary level, furthermore assess the perfusion status of tissues or organs.Therefore, using the scanning technique of320-slice CT to analyze the perfusion images of ALI can reflect the inflammatory disease process of ALI objectively and dynamically, which may help to clarify the possible pathogenesis. The ulinastatin is an urinary trypsin inhibitor isolated from male urine, which is a glycoprotein with typical protease inhibitor structure of Kuniz and there two completely non-overlapping active function area.All of them have a broad spectrum of enzyme inhibition activity. Ulinastatin binds with a variety of enzyme sites by competitive binding with the binding site of the enzyme substrate and the noncompetitive inhibition, which can be simultaneously inhibit a variety of hydrolase activity including trypsin, hyaluronidase, elastase and phospholipase A2and so on.The enzyme inhibiting ability of the degradation products is stronger. Ulinastatin can inhibit the production of myocardial inhibit cytokine, stable the lysosomal membranes, inhibit the release of inflammatory mediators, and improve the microcirculation of shock.Using ulinastatin as the drug intervention and comparing the perfusion images between before and after intervention/inflammatory markers/pathological findings and so on, which can be further explore the inflammatory mechanism of acute lung injury and provide experimental basis for clinical treatment.Methods30New Zealand white rabbits were randomly divided into a control group, a paraquat group and an ULI intervention group with10rabbits in each group. For paraquat group and intervention group a single dose of paraquat (35mg/kg) was injected intraperitoneally to establish rabbit models of ALI. The control group was injected an equal volume of saline. The intervention group was treated with100Ku/kg ulinastatin immediately after the establishment of the ALI model. All the experimental groups underwent320-slice CT perfusion scan of pleural at2h,4h and6h after modeling to get CTP (CT Perfusion) images and related parameters, which including the regional permeability surface(rPS)/the regional blood volume(rBV) and the regional blood flower(rBF).2ml blood was collected in the marginal ear vein to determine the mass concentration of the vascular endothelial growth factor (VEGF). Animals were sacrificed by air embolism and obtained the lung tissues for pathological exam after6hour.ResultsThe regional blood flow (rBF) and regional blood volume (rBV) of paraquat group at2,4,6h time point were significantly (P<0.05) lower than those of control group. The intervention group rBF and rBV at2,4and6h time points were significantly higher (P <0.05) compared to the paraquat group. The VEGF mass concentrations and the permeability surface (rPS) of paraquat group at2,4,6h time point were significantly higher than the control group (P<0.05), and the intervention group VEGF mass concentrations and rPS at2,4,6h were significantly lower (P<0.05) than those of paraquat group. Pathological detection indicators of paraquat group (congestive capillary percentage, the number of red blood cells outside of capillaries, percentage of capillaries with basement membrane damage) were significantly higher (P<0.05) at6h compared with the control group, but significantly lower (P<0.05) in intervention group than in paraquat group. The main pathological changes of PQ group by microscopic examination were inflammatory granulocyte infiltration, alveolar epithelial cell proliferation, disseminated thickening of alveolar septa, local hemorrhages and the lumen of acute and chronic inflammatory cell infiltration; under electron microscopy alveolar epithelial cell degeneration and necrosis, vascular welling of the endothelial cells, basement membrane rupture, a lot of exudates in alveolar space. In the intervention group, the above symptoms were mitigated.ConclusionsIn the early stage of rabbit ALI induced by PQ, pulmonary vascular endothelial cell is damaged and the serum VEGF mass concentration and pulmonary vascular permeability increase. Early ULI intervention can reduce serum VEGF level and PQ-induced vascular permeability amplitude, which means that ULI has a protective effect on pulmonary vascular endothelial cells.320-slice CT can be applied to the study of acute lung injury.