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Research background and purpose of severe acute pancreatitis (Severe acute pancreatitis, SAP) today Pancreatology problem, the source of its rapid onset of severe illness, and rapid development, often appear early acute complications, the mortality rate as high as 20% to 40% , so long Gastroenterology and Surgery Research focus and emphasis. Although treatment technology continues to improve, but still difficult to reverse the high mortality of SAP, rapid progress of the disease characteristics. Early stage of SAP leading cause of death due to multiple organ dysfunction syndrome (Multiple organ dysfunction syndrome, MODS) systemic inflammatory response syndrome (Systemic inflammatory response syndrome, SIRS), a variety of inflammatory cytokines, particularly TNF-a as SAP The earliest to produce proinflammatory media played in the SAP concurrent the SIRS to enter MODS process important role. Therefore, some scholars have proposed SAP progression to MODS stage there is the \In recent years, with patients with severe acute pancreatitis complicated by intra-abdominal hypertension (intra-abdominal hypertension IAH) and abdominal compartment syndrome (abdominal compartment syndrome, ACS) clinical reports of increasing intra-abdominal pressure (intra-abdominal pressure, IAP) pathological elevated IAH and ACS, leading to multiple organ dysfunction heavier SAP patient's condition, the mortality rate is extremely high. It is currently reported in the literature SAP patients with intra-abdominal hypertension incidence by about 40% appear the ACS from about 10% the SAP if accompanied by ACS dangerous disease, the fatality rate as high as 60% to 70%. Will cause the body now recognize that SAP has concurrent IAH IAH elevated pathophysiological changes, IAH and SIRS both intertwined with each other to promote and accelerate the process of MODS. The early detection of IAH, and take active conservative treatment or surgical decompression treatment options can reverse the further development of the ACS to reduce the mortality of SAP. View of MODS the early main causes of death in patients with SAP, the direct causal relationship between SAP and IAH and organ failure so far not yet clear, the current is very necessary to prepare a clinically relevant animal model, in particular, to carry out the pathological induction of SAP and MODS and IAH / ACS ideal animal model related to the pathophysiology and prevention studies. Currently, there are reported sodium taurocholate (NaTc) retrograde induced acute necrotizing pancreatitis (Acute necrotizing pancreatitis ANP) rat model can lead to multiple organ damage; scholars first reported in 2007, 3.5% taurocholic induced by sodium cholate ANP model may be complicated by multiple organ pathological changes for SAP and the MODS the ideal model, but did not carry out the multi-group concentration of research and comparison. The ideal SAP, and MODS animal model should have the morphological changes in the course of disease and response to treatment with human SAP, and has a higher incidence of MODS and higher survival rates. Therefore, we first carry out multiple concentrations of taurocholate sodium cholate retrograde establishment of the ANP and MODS model to seek a higher incidence of MODS and a higher survival rate of the optimum concentration model, at the same time, the detection of intra-abdominal pressure groups model group and control group , TNF-a phase change, focus on observation of the optimum concentration of sodium taurocholate-induced model of ANP in intra-abdominal pressure and TNF-a phase change its laws. Our experimental research concrete is divided into the following two parts: (a) severe acute pancreatitis and MODS model in rats: carry out multiple concentrations of taurocholate sodium cholate retrograde induction of ANP and MODS model, seeking a higher incidence of MODS and higher survival rate of animal models prepared ANP complicated with MODS ideal animal model, and provide an experimental basis for further study of the SAP pathogenesis and drug research intervention SAP complicated with MODS. (B) severe acute pancreatitis and MODS rat model of intra-abdominal pressure, TNF-a phase change research: Based on the experimental basis of the study, 1h, 3h, 6h, 12h, 24h dynamic observation of the best concentration of cattle sulfonamide gall sodium ANP rats model of intra-abdominal pressure induced phase changes in TNF-a serum amylase, pancreatic pathology score, to investigate the severity of pancreatitis lesions with intra-abdominal pressure, TNF-a relationship for the future SAP concurrent IAH / ACS The study experimental basis. Method (a) of severe acute pancreatitis and MODS model in rats: cholangiopancreatography retrograde injection NaTc preparation ANP model 280, were randomly divided into a control group (40), and 3.5%, 4%, 4.5%, 5% ANP group (n = 60). Each model group, 40 rats in 1,3,6,12,24 h after modeling were used to detect serum amylase, total bilirubin, creatinine, blood gas analysis, and pancreatic pathology; another 20 rats were observed after modeling 24h survival. (B) severe acute pancreatitis and MODS rat model of intra-abdominal pressure, TNF-a phase change studies: 40 ANP model prepared by retrograde injection of 4.5% sodium taurocholate into the pancreatic duct, the control group was injected with the same amount physiological saline in each group at 1h, 3h, 6h, 12h, 24h time point, eight rats were sacrificed, the dynamic of serum amylase, TNF-α, ascites, intra-abdominal pressure and pathological changes of pancreas. (A) severe acute pancreatitis and the MODS rat model preparation: ① The model group, serum amylase, liver, kidney and respiratory function indicators the Sui NaTc concentration and molding time was a significant dose - and time - effect relationship . ② The model group at all time points pancreatic pathology score was significantly higher than that of the control group. 3 4.5 group liver and kidney dysfunction peak at 6h, 12h peak of respiratory dysfunction MODS was 52.5%; 24h survival rate was 65%, significantly higher than 30% of the 5% group. (B) severe acute pancreatitis and MODS rat model of intra-abdominal pressure, TNF-a phase change research: ① ANP group of blood amylase was progressively increased, and were significantly higher than at the same time point the control group; ② ANP group rats from 1h start intra-abdominal pressure, and was progressively increased 3h approximately three times the control group; 12h peaked about nine times that of the control group; ③ The serum TNF-α mean higher than the control group at the same time point, 6h up peak; The ④ ANP group appeared to rats 1h pancreatic pathology score significant difference, 3h pancreatic necrosis peaked at 24h. Conclusion 1 sodium taurocholate induced ANP and the MODS model of amount - activity relationship studies, 4.5% sodium taurocholate induced ANP and the MODS model of ideal concentration, the incidence of MODS model and 24h survival rates were 52.5% and 65%. Optimal induction concentration when - activity relationship studies show that 4.5% of ANP exist obvious intra-abdominal hypertension in rats 6h reaction peak point in time for the inflammatory mediators TNF-α, intra-abdominal pressure may their subsequent reaction.
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