The Expression Of Toll Like Receptor 4 In Liver, Intestinal Mucosa In Rats With Pancreatical Sepsis And It's Relevancy To Multiple Organ Dysfunction

[Background] The acute pancreatitis varies from mild to severe. Mild pancreatitis presents as a self-limiting disease with low morbidity and mortality (<1%).In about 15% to 20% of cases pancreatitis are severe pancreatitis. The natural course of severe acute pancreatitis progresses in two phases. The first 14 days after onset of the disease are characterized by the systemic inflammatory response syndrome (SIRS). Infection of pancreatic necrosis in the second and third week after onset of the disease is reported in 40% to 70% of patients with severe pancreatitis. Today,only a few part of patients with severe acute pancreatitis die of SIRS-associated complications, because diagnostics and intensive care therapy have been improved progressively. Sepsis- related multiple organ failure induced by infected pancreatic necrosis is the main life-threatening complication, with a mortality rate of up to 50%.It is proved that intestinal bacterial translocation is the cause of pancreatic infection. TLR4 as the critical pathogen-recognition receptor and the only transmembrane protein of lipopolysaccharide is identified to mediate immune response and inflammatory response.[Objective] On the basis of pancreatic sepsis model in rats, to explore the changes and significances of TLR4 in liver and intestine in the development of multiple organ dysfunction.[methods] One hundred male Wisdar rats were divided into three groups:Groupsham (n=24) received only puncture of pancreatic duct,Group NaTc (n=37) receivedretrograde injection of 3.5% taurocholate into pancreatic duct, Group NaTc+LPS(n=39) received intraperitoneal injection of LPS in rats preexisting retrogradeinjection of 3.5% taurocholate into pancreatic duct after 2h. Mortality andtime-course changes in pancreatic, hepatic, renal, pulmonary and intestinal functions were examined;TLR4mRNA and TLR4 in the liver and intestine were detected by in situ hybridization and immunohistochemistry.The MPO in pancreas,TNF a in serum and SIgA in intestinal tract were also detected.[Results] Pancreatic sepsis model was successfully induced in Wistar rats.Compared with sham and NaTc rats,NaTc+LPS group resulted in significant increase the severity of pancreatic, hepatic, renal, pulmonary and intestinal injury;elevation of serum GOT, GPT,BUN, amylase and TNF a levels;up- regulated hepatic TLR4 expression;down- regulated intestinal TLR4 expression and decrease SIgA in intestinal tract.[conclusion] This is a adaptive model to mimic the course of human severe pancreatitis;septic complications associated with pancreatitis promote the development of multiple organ dysfunction;TLR4 plays a important role in the pathogenesis of this course.