The Therapeutic Effect And The Mechanism Of RhUTI To Acute Pancreatitis(AP) In Mice And Beagle Dog

Research BackgroundAcute pancreatitis(AP) is a common disease. The pathogenesis of AP and AP damage control method has become a hot and difficult medical issue. Recent research has found that early use of ulinastatin (UTI) treatment of AP, the patient's symptoms and signs have improved the high cure rate with few complications. UTI can inhibit the release of enzymes related to pancreatitis development, control the development of pancreatitis and prevent pancreatitis from mild to severe, which has played better clinical therapeutic effects.Object We study the RhUTI protective effect in mice AP model and Beagle dog AP model, to explore whether rhUTI has treatment effects to AP model animals, and its possible mechanism, in order to provide a theoretical basis for clinical application declaration of new drugs.Method1 MiceExperimental mice were randomly divided into six groups: control group, AP group, UTI Group(45U/g), rhUTI low-dose group(22.5U/g), rhUTI middle dose group (45U/g)and high dose group rhUTI (90U/g), twice 1h interval high-dose intraperitoneal injection of L-arginine (2×200mg×100g-1 body weight) to duplicate AP model mice. After the experiment, by chemical colorimetry, we detect serum amylase and pancreatic tissue superoxide dismutase (SOD) activity and malondialdehyde (MDA) content; take pancreatic tissue fixation, HE staining to observe pathological changes of the pancreas.2 Beagle dogExperimental Beagle dogs were randomly divided into six groups: control group, AP group, UTI Group(15U/g), rhUTI low-dose group(7.5U/g), rhUTI middle dose group(15U/g) and high-dose group(30U/g). We use retrograde sodium taurocholate (2.5%) of pancreatic duct injection Ways to create Beagle dogs AP model. After the experiment, by chemical colorimetry, we detect the animals serum amylase and urine amylase changes; use MODULAR-DPP type automatic biochemical analyzer to detect serum Ca²⁺, BUN, Cr changes; take pancreatic tissue fixation, HE staining to observe the pathological changes of the pancreas.Result1.The protective effect of rhUTI to AP in miceHigh-dose intraperitoneal injection of L-arginine (2×200mg×100g-1 body weight) can cause elevated serum amylase; pancreatic congestion and edema, inflammatory cell infiltration and a small building of necrosis, acute pancreatic replication in mice Successful inflammation model. Compared with the control group, AP mouse serum amylase level was significantly increased(P<0.05), pancreatic tissue superoxide dismutase (SOD) activity(P<0.05); pancreatic tissue malondialdehyde (MDA) content increased(P<0.05). Compared with model group, UTI, and different rhUTI dose groups congestion and edema reduced, necrotic foci decreased to reduce inflammatory cell infiltration, serum amylase 12h, 24h significantly lower than the model group ( P<0.05 ) ; SOD activity increased and MDA content decreased significantly(P<0.05). 2 The protective effect of rhUTI to AP in beagle dogRetrograde sodium taurocholate (2.5%) pancreatic duct injection can cause Beagle dog serum amylase, urine amylase increased congestive pancreatic tissue edema, necrosis, acute pancreatitis induced by the success of Beagle dogs; with the control group, AP Beagle dog serum amylase and urine amylase were significantly higher(P<0.05), Serum Ca²⁺ concentration, serum creatinine concentration in the model reduced after 8h. Compared with the AP model group, UTI, and medicine rhUTI positive serum amylase 8h, 24h significantly lower than the model group(P<0.05), urine amylase level decreased significantly(P<0.05), and there is dose-dependent relationship; rhUTI (0.75,3 million U / kg) of acute pancreatitis model in dogs after 4h, 8h certain blood urea nitrogen increased, rhUTI (15,30U/g) group after the model 28h, serum Ca²⁺ concentration reduced. Compared with the model group, UTI, and the dose group rhUTI reduce congestion and edema, necrotic foci decreased to reduce inflammatory cell infiltration.Conclusion For sodium taurocholate-induced AP in Beagle dogs and L-arginine-induced AP of pancreatic injury in mice, rhUTI has a protective effect, and its mechanism may has relationship with the following factors: increased SOD activity by rhUTI, lower MDA content, and removal of oxygen free radicals..