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The Test On The Role Of Nuclear Factor-kappaB Activation On Acute Lung Injury Of Acute Necrotizing Pancreatitis

Posted on:2004-07-06Degree:DoctorType:Dissertation
Country:ChinaCandidate:W ZuoFull Text:PDF
GTID:1104360092495848Subject:Surgery
Abstract/Summary:PDF Full Text Request
The therapy of acute lung injury ( ALJ) is a difficult task in respiratory system disease. Though much work have down on it, the morbidit and mortalit of ALI is still high. ALI is a common complication of acute necrotizing pancreatitis ( ANP). Up to 70% of ANP patients have detectable sign of ALI. Many of them developed into adult respiratory distress syndrome ( ARDS). It is the main cause of death at an early stage of ANP. Much study indicates that the over production of cytokines is connect with ALI in ANP, but there are many work should do on the pathogenesis of ALI in ANP. Nuclear factor - kappaB ( NF -kappaB) is member of Rel transcription regulator protein. It include p50, p52, p65, c - Rel, Rel B etc. NF - kappaB is a heterodimer or homodimer that can be found in the cytoplasm of most cells as inactive complex binding with I?B. IKB can be degraded by some stimulating agents and NF - kappaB activated. NF- kappaB entered nuclei and bond with KB site on promoter of many genes. NF- kappaB can regulate the expression of many inflammatory genes such as TNF- a, IL - 6, - 8, and inducible nitric oxide synthase ( iNOS) . These cytokines involved in the pathogenesis of ALI in ANP. Nitric Oxide ( NO) is a molecule that participated in the pathophysiology of infection, immune, vessel disease. High level of NO can lead to the over production of free radical thus lead to ALI. With the development of the study on NO, the role of NO in ALI in ANP was deeply investigated. More and more study indicates that the NO plays a key role hi the pathogenesis of ALI in ANP. Octreotide is a semisynthetic analogue of somatostatinand used in the therapy of ANP. The role of octreotide has always been considered to be due to the inhibition of the exocrine pancreatic secretion in order to reduce pancreatic autodigestion and was deeply investigated. Whereas the role of octreotide in the pathogenesis of ALI in ANP has not beenseen. We use the model of ANP and study the role of NF - kappaB activation on the pathogenesis of ALI in ANP, the role of NF - kappaB on NO in ALI in ANP, and the role of octreotide in the pathogenesis of ALI in ANP.METHODSANP Model preparation: We randomized male Wistar rats, with weights ranging from 250g to 300g, ANP model was induced by slow and even infusion of 5% sodium taurocholate 0. 001mg/g in pancreatic duct, whereas control group received an infusion of physiological saline of the same amount. Part I, the rats was randomized into three groups Control group, ANP group, and pyrro-lidine dithiocarbamate ( PDTC) group. In addition to sodium taurocholate, PDTC group received intravenous infusion of PDTC 0. 01mg/g, while Control and ANP group received the same amount of physiological saline solution instead. At 3, 6, 12 hours of the model each group select 10 rats and detect the change of serum amylase, PaO2, the pathology of pancreas and lung, the expressioni
Keywords/Search Tags:Pancreatitis,Acute Necrotizing, Acute Lung Injury, Nuclear Factor-kappaB, Nitric Oxide, Octreotide
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