Protection Effect And Mechanism Of Ulinastatin On Acute Necrosis Pancreatitis In Rats

Backgroud：Acute pancreatitis (AP) is an acute inflammation of the pancreas thatattributes to various factors which activate the pancreatic enzymes, result in digestion,edema, hemorrhage and inflammationary necrosis of pancreas. Although the majority ofpatients have a mild episode of AP with good prognosis, some still develop the SAP andsuffer the systemic inflammatory response syndrome(SIRS), with the multiple organdysfunction syndromes(MODS), even leads to death. However, the pathogenicmechanisms in SAP are not completely understood. In recent years, the incidence of acutesevere pancreatitis were rising trend. However, clinical treatment measures on pancreatitiswere not effective enough due to unclear pathogenesis of pancreatitis.Autophagy is the new way of cell death in recent years. With the constantunderstanding of autophagy, autophagy is thought to be closely related to the occurrenceand development of various diseases. The study of autophagy in acute pancreatitis wasgradually increased, indicating that autophagy body in acute pancreatitis increased andabnormal autophagy were related to the activation of enzyme precursor. So we speculatedthat inhibition or blockade of autophagy occurrence and development may be a potentialtarget for the treatment of acute pancreatitis. Protease inhibitors ulinastatin applied tointervention of acute necrotizing pancreatitis are studied in our experiment to explore theprotective effect and related possible mechanisms.Aims：In order to explore Protection effect and the related mechanism of Ulinastatinon acute necrosis pancreatitis（ANP）in rats.Methods：The animal model of ANP was established by retrograde injection of5%sodium taurocholate (1ml/kg) into pancreaticbiliary duct with its proximal end clampedgently. Rats were sacrificed at3,6,12hours after establishment of ANP, respectively. TheFifty-four Sprague-Dawley (SD) rats were randomly divided into sham operation group(SO group), ANP group and UTI-treated group. In the UTI-treated group, UTI2.5ml(l00000U/kg,12500u/ml, the rate of0.2ml/min)was given intravenously through tail veininjection after ANP model is set up30minutes later. SO and ANP group were given thesame amount of saline solution by tail vein injection; Sertum level of amylase (AMY) wasdetermined by automatic biochemistry analyzer, interleukin (IL)-1β was measured byELISA. Pancreatic histopathological changes were observed by HE staining. Expressionsof Beclin-1and NF-κ B in pancreas were detected by immunohistochemistry and Westernblotting.Results：Compared with SO group, serum levels of AMY and IL-1β, pancreaticpathological changes expressions of Beclin-1and NF-κ B in ANP group were increased ina time-dependent manner (P<0.05). At6th,12th hour, serum levels of AMY and IL-1β,pancreatic pathological injury and expressions of Beclin-1and NF-κ B in UTI group weresignificantly decreased than those in ANP group(P <0.05)。Moreover, serum levels ofAMY and IL-1β were significantly decreased in UTI group than those in ANP group(P<0.05). Pathological injury and expressions of Beclin-1and NF-κ B were significantlydecreased at12th hour(P<0.05).Conclusion：Ulinastatin on rats with acute necrotizing pancreatitis has certainprotective effect. The mechanism may be through blocking autophagy activation andinflammatory cascade, in addition to the inhibition of various protease activity.