The Pathogenesis Of The Experimental Acute Necrotzing Pancreatitis Combined With Lung Injury In Rats And The Effect Of Treatment With Glutathione

The pathogenesis of the experimental acute necrotzing pancreatitis combined with lung injury in rats and the effect of treatment with Glutathione. Postgraduate: zhang yu-hui tutor: wu lin-quan Objective The mechanism of lung injury associated with acute necrotizing pancreatitis remains unclear .The present studies observed lung injury model of acute necrotizing pancreatitis rats induced by intraductal of 5% sodium taurocholate and pay attention to the change such as the role of NF-κB and TNF-α in lung injury. To explore the pathogenesis of experimental acute necrotizing pancreatitis combined with acute lung injury (ALI) in SD rats , whether the treatment with antioxidant Glutathione would ameliorated the lung injury or suppress the activation of NF-κB. Methods The establishment of rats model , 250g～300g Sprague-Dawley male or female rats were used. Total of 90 rats were randomly divided into three groups: ANP model group(Ⅱgroup ,n=30) and Glutathione treatment group (Ⅲgroup, n=30) were induced by the retrograde intraductal infusion of 5% sodium taurocholate(0.1ml/100g) with its proximal end clamped gently. While the Normal control group (Ⅰgroup, n=30) received laparotomy and smooth the pancreas tissue some times only. TheⅢgroup were injecting 6% Glutathione(1ml/100g) intravenously at 1st hour after ANP model was induced. The Ⅰgroup andⅡgroup were injecting 0.9% NS (1ml/100g). Then the three groups were divided into 3 hour group ,6 hour group ,12 hour group according to different time, each was ten. All rats were killed at 3th ,6th and 12th hour after model was induced respectively. Severity of ANP was determined by measuring plasma amylase, serum TNF-α and activity were analyzed. Lung injury was determined by measurement lung water content, The arterial blood gas, lung lipid peroxidization. myeloperoxidase (MPO) activity as a measure of neutrophil sequestration in the lung tissue. The lobe of rat lung was dissected for histology and lung tissue myeloperoxidase (MPO), peroxidization (MDA) checking . The NF-κB detected with immunohistochemistry and histological appearance of lung and pancreas were observed under microscope . Results At the 6th and 12th hour ,All the parameters of Ⅱgroups compared to Ⅰ group had the statistical significance (P<0.05). The lung injury of ANP rats was gradually aggravated along with disease progression. The level of MDA , MPO of lung tissue and generation of TNF-α manifested a steady significant increase with time. All indicators of Ⅲ group were elevated compared with the Ⅰ group, but they were all decreased and arterial gas,MDA ,MPO had statistical significance compared to Ⅱ group(P<0.05). The histology scores results definitively demonstrated lung damage was becoming more serious with time and had statistical significance with the Ⅰ group. compared with Ⅱ group, to treatment with Glutathione could prevent lung injury, the histology score were remarkly decreased. Activation of NF-κB were almost absent in Ⅰgroup but remarkably increased in Ⅱ group rats, the degree of NF-κB activated was decreased in Ⅲ group as compare with Ⅱ group.Conclusion　 Lung injury is the most early complication associated with ANP. NF-κB could be activated in ANP, Large amounts of Inflammatory mediators were released, then caused the lung injury . The experiment study showed that the activation of NF-κB may be the important way of lung injury of ANP. Activation of NF-κB and NF-κB-mediated cytokine expression is one of the main factors for acute lung injury in ANP. Treatment with antioxidant Glutathione can significantly Ameliorated the lung injury associated with ANP in rats.