The Research Of Angiopoietin-like Protein 3 In Hyperlipidemic Acute Pancreatitis

Part ⅠThe establishment of rat hyperlipidemic acute pancreatitis modelObjectiveTo establish a stable rat model of hyperlipidemic acute pancreatitis and investigate its pathophysiology. To explore the effect of hyperlipemia on pathogenetic condition of rats with acute pancreatitis.MethodsEighty rats were randomly divided into 4 groups: 20 in control group, 20 in HL group, 20 in SAP group and 20 in HLAP group. Rats underwent intragastric administration of self-make high fat diet two weeks to establish the models of hyperlipemia. 3.5% sodium taurocholate was retrograde injected into the pancreatic duct to induce severe acute pancreatitis. The general condition of rats of each group was observed. Blood and pancreatic tissue of rats in each group were collected 6hours after the models were established. The level of serum triglyceride, cholesterol and amylase were detected. The histopathologic damage degree of pancreas were observed.ResultsThe level of serum triglyceride and cholesterol in HL group and HLAP group were higher than control group and SAP group(p<0.01). The serum amylase level in SAP group and HLAP group were significantly higher than control group and HL group. The level of serum amylase in HLAP group was significantly lower than in SAP group( p<0.05). Histological examination suggested that pancreatic tissue showed severe inflammatory cell infiltration, hemorrhage and necrosis. The necrosis scores significantly increased in HLAP group than in SAP group(p<0.05).ConclusionThe rat model of hyperlipidemic acute pancreatitis could be established successfully by the combination of intragastric administration with high fat diet and3.5% sodium taurocholate retrograde injected into the pancreatic duct. The pathogenesis and pathological manifestations in this rat model were similar to those in human with hyperlipidemic acute pancreatitis. The rat model has the characteristics of high success rate, short production cycle, good feasibility and so on. Hyperlipemia could aggravate the pathological damage of pancreatic tissue in rat with acute pancreatitis.Part ⅡThe study of angiopoietin-like protein3 in rat hyperlipidemic acute pancreatitisObjectiveTo explore the relationship between angiopoietin-like protein3 and rat hyperlipidemic acute pancreatitis and observe the effect on rat hyperlipidemic acute pancreatitis after up-regulating the expression of angiopoietin-like protein3.Methods120 rats were randomly divided into 6 groups: 20 in control group, 20 in HL group, 20 in SAP group, 20 in HLAP group, 20 in drug HL group and 20 in drug HLAP group. Rats underwent intragastric administration of self-make high fat diet two weeks to establish the models of hyperlipemia. 3.5% sodium taurocholate was retrograde injected into the pancreatic duct to induce severe acute pancreatitis. The general condition of rats in each group was observed. Liver, blood and pancreatic tissue of rats of each group were collected 6 hours after the models were established.The level of serum triglyceride, cholesterol and amylase were detected. The histopathologic damage degree of pancreas was observed. Real time real-time fluorescence PCR was used to detect the expression of angiopoietin-like protein3 in liver and ELISA was used to detect the level of serum ANGPTL3 protein in rats.ResultsThe expression of angiopoietin-like protein3 in rat liver of HL group and HLAP group elevated significantly than the control and SAP group(p<0.01). The level of HLAP group was higher than the HL group( p<0.05). The expression of liver angiopoietin-like protein3 and serum ANGPTL3 protein was significantly higher than HL group and HLAP group(p<0.01). But the expression of ANGPTL3 between drug HL group and drug HLAP group was undifferentiated(p>0.05). The level of serum triglyceride and cholesterol in drug HL group and drug HLAP group were higher than in HL group and HLAP group(p<0.05). The serum amylase level in HLAP group and drug HLAP group were significantly higher than those in HL group and drug HL group(p<0.01). The level of serum amylase was undifferentiated between drug HLAP group and drug HLAP group( p<0.05). Histological examination suggested that pancreatic tissue showed severe inflammatory cell infiltration, hemorrhage and necrosis in both HLAP group and drug HLAP group.The necrosis scores significantly increased in drug HLAP group than in HLAP group(p<0.05).ConclusionRats Angptl3 genes and HLAP has certain relevance. Rat model in HLAP group expressed higher level of ANGPTL3. T0901317 can raise the expression of Angptl3 gene in rats and aggravate the necrosis of pancreatic tissue in HLAP.PartⅢ The role of insulin in the therapy of hypertriglyceridemic acute pancreatitis patients.ObjectiveTo assess the correlation of insulin lipid-lowering effect with the prognosis and the expression of angiopoietin-like protein3 in hypertriglyceridemic acute pancreatitis.MethodsRetrospective the results of forty patients were admitted to our hospital with hypertriglyceridemic acute pancreatitis, All patient’s with triglyceride levels >5.65mmol/l when admission,According the blood glucose levels divide into Regular Insulin(RI) and Conventional treatment groups. The day of decline triglyceride levels below 5.65mmol/l、abdominal pain deprivation and recovery of intestinal function; complications and time of discharge were observed. ELISA was used to detect the level of serum ANGPTL3 protein in HLAP patients.ResultsTimes courses of decline triglyceride levels below 5.65mmol/l、abdominal pain disappear and recovery of intestinal function were respectively,(3.41±1.74),(3.64±1.43) and(8.09±2.81) days in RI group,and(5.89±1.37),(5.28±1.36) and(10.00±2.72) days in Conventional treatment group,the differences were significant between the two groups(p<0.05);But there is no significant difference concerning the average length of hospital stay respectively was( 31.1±28.2) d with(19.7±6.1)d、complications and fatality rate in RI and Conventional group(p>0.05).One patient in RI group died of secondary fungal infection. The level of ANGPTL3 protein in the serum of patients was no difference between the RI group and Conventional treatment group when they were hospitalized(p>0.05). After treatment, the level of ANGPTL3 protein in the serum of patients decreased significantly in both RI group and Conventional treatment group(p<0.01). The level of ANGPTL3 protein in RI group was significantly lower than the Conventional treatment group after treatment(p<0.05).ConclusionFor patients with hypertriglyceridemia acute pancreatitis, intravenous infusion of insulin could fastly decline the levels of triglyceridemia,improve the symptoms of early phase,but can’t shorten the time of stay and improve prognosis. Otherwise intravenous infusion of insulin could reduce the level of serum ANGPTL3 protein concentration in HLAP patients.