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The Role Of Nuclear Factor-KappaB Activation In The Lung Injury Of Murine Acute Necrotizing Pancreatitis

Posted on:2004-09-23Degree:MasterType:Thesis
Country:ChinaCandidate:Z G LuanFull Text:PDF
GTID:2144360092495967Subject:Surgery
Abstract/Summary:PDF Full Text Request
IntroductionStudies recently indicate that nuclear factor (NF - KB) is a important transcription factor. It plays a core role in the transcription regulation of cell information medicated by kinds of exo - cell stimulations. When activated NF - KB bind with KB ranks (5 ' - GG-GACTTTCC -3") in the gene promoters and enhancer, it can take part in the expression and regulation of many kinds of genes that specially relating to body defensively responsive immediate - early genes such as cytokine and inflammatory factors and it will be envolved in the genesis of the acute inflammatory reaction and play a good action in ihe development of diseases.Many agents can induce the activation of NF - KB. The anterior inflammation mediums such as TNF - a,IL - 1 and ROI are the powerful inducers of NF - KB and virus, bacterial lipopolysaccharide ( LPS) ,PMA can activate NF - KB, too. Antioxidant for example N -acetylcysteine,pyrrolidine dithiocarbamate (PDTC) can inhibite the activation of NF - KB by the induction of ROI and the connection with DNA. Experiments both in vivo and in vitro have detected that antiox-idant ( NAC,PDTC) can inhibite the activation of NF - KB.The fatality of acute necrotizing pancreatitis in the seven days of early age episode is sixty perent related to acute respiration failure. This kind of respiratory failure is hard to differentiate with the respira-tion failure that is complicated with hematosepsis and burn. It is an a-cute diffuse injury of endothelium and germinal epithelium of lung tissue. The respiration failure mainly manifest the increases of lung wet weight ,permeability of alveoli blood capillary , lesion of alveoli endo-thelial cell and lung Interstitial , aggregation of neutrophil and so on. These occurrences are intimatly related to cytokine.The cytokine in the lung tissue are generated by alveolar macro-phage, alveoli cell, fibroblast, endothelial cell, retention neutrophil, lymphocyte and blood platelet in the lung. The network disequilibrium of cytokine and the aggregation of ultra - activation neutrophil in the lung are main causes of ANP induced acute lung injury. It is well known that NO is a free radical. Left - handed rotation arginine is the substrate to synthesize nitric oxide during the course of the nitric oxide synthase catalysis. Recently investigations show that the level of cytokine rise in the acute necrotizing pancreatitis and the latter induce the generation of nitric oxide. Nitric oxide possiblely take part in the development of the progress of pancreatitis and total body complications. Some scholars have the point that nitric oxide is an important factor in the course of acute necrotizing pancreatitis that result in multiple organ failure.Some studies show in the earlier period of acute necrotizing pancreatitis endotoxemia will be found, the endotoxin will induce the extra - generation of cytokine and the ultra - expression of nitric oxide. So it will generate the cytotoxicity that maybe result in multiple organ injury. Nitric oxide may have a key role in the pathologic and physiologic course of acute necrotizing pancreatitis. NF - KB regulate the gene expression of inflammatory factor. Therefore, the methods of inhibiting the activation of NF - KB will be an important measurement toprevent the development of acute pancreatitis.ObjectiveTo investigate the possible role of nuclear factor - KB ( NF -KB ) activation in the lung injury of murine acute necrotizing pancreatitis (ANP) and assess the potential beneficial effects of pyrrolidine dithiocarbamate (PDTC) , an inhibitor of NF - KB.MethodsRat ANP model was estabilished by retrograde injection of 5% sodium taurocholate into choledochopancreatic duct. Rats were divided into four groups, Control group, ANP group, and PDTC1 2 groups. The changes of serum amylase, patial pressure of arterial oxygen ( PaO2) , albumin Content of bronchoalveolar lavage fluid, activity of myeloperoxidase, pancreas and lung morphological damage were observed. The expression of NF - KB and induci...
Keywords/Search Tags:Acute Pancreatitis, Lung Injury, Nuclear Factor -kappaB
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