Experimental Study On Changes Of Serum Cytokines And Treated Effect Among Them By 5-Fluorouracil And Octreotide In Acute Phase Of Acute Pancreatitis In Rats

Objective:Experimental stady on the changes of serum level of TNF-a, IL-6,IL-10 and IL-4 in acute phase of acute pancreatitis in rats and to observe the changes of serum level of these cytokines under the treatment of 5-fluorouracil (5-Fu) or octreotide (Oct) so to evaluate the therapeutic effect in acute necrotizing pancreatitis.MethodsrAcute edematous pancreatitis (AEP) and acute necrotizing pancreatitis (ANP) models were established by the injection of 1% or 5% sodium taurocholate(0.1ml/100g) into the common choledocho-pancreatic duct respectively in male SD rats.A total of 80 SD rats were randomized to five equal groups:Sham group(control group):the rats were received normal saline injection (0.1ml/100g) into their common choledocho-pancreatic duct;AEP group;ANP group;5-Fu group,30 minutes after induced ANP model,the rats were received 5-Fu(4.5mg/100g) through their femoral vein; Oct group,30 minutes after induced ANP model,the rats were received octreotide(0.9?g/100g) through their femoral vein.The half of the studied rats were sacrificed at 3 hours and another half at 6 hours in each group after establishment of the studied model.The following parameters were determined: serum amylase,macroscopic pathologic scoring of the lung and pancreas,pancreatic histological pathologic scoring, amount of ascites and serum levels of TNF-?,IL-6,IL-10 and IL-4. ResuIts:The content of serum amylase was significantly increased in both AEP and ANP groups,of which much higher level In ANP group (P<0.01),than that of sham group (P<0.01).The pancreatic and lung macroscopic pathologic scoring,the pancreatic histological pathologic scoring and the amount of ascite at 6 hours were significantly higher in ANP group than those in AEP group with P<0.01,P<0.001,P<0.05 respectively. The serum levels of TNF-?,IL-6 and EL-10 were significantly higher than those in sham group with P<0.001, P<0.001, P<0.001 respectively.The serum TNF-? at the 6 hours and the serum IL-6 and IL-10 at the 3 and 6 hours in ANP group were all significantly higher than in AEP group with P<0.05,P<0.001 ,P<0.05 and P<0.05, P<0.05 respectively. In ANP group,the levels of serum TNF-? and IL-6 at 6 hours were significantly higher than those at3 hours with P<0.05, P<0.05 respectively. In 5-Fu group ,the serum amylase and the pancreatic histological pathologic scoring at 3 hours and the amount of ascites at 6 hours all were decreased significantly with P<0.01,P<0.05, P<0.05 respectively.While the pancreatic and lung macroscpic pathologic scoring,the serum amylase level and pancreatic histological pathologic scoring at 6 hours determination and the amount of ascites at 3 hours were not significant. The serum levels of TNF-? and IL-10 both at 3 hours (P<0.05,P<0.001) and at 6 hours (P<0.05, P<0.05) all were decreased.While serum IL-6 at 6 hours was decreased (P<0.01). In Oct group ,the content of serum amylase, the both pancreatic and lung macroscopic pathologic scoring and pancreatic histological pathologic scoring revealed no improvement. While the amount of ascites at 6 hours was decreased (P<0.05).The level of serum TNF-? was significantly decreased (P<0.01) , In addition it was apparently lower than in 5-Fu group at 6 hours (P<0.01).There were no change in the level of serum IL-6 and IL-10.The level of serum IL-4 revealed no statistical difference in all groups. Conclusions:The cytokines(TNF-?,IL-6,IL-10) play an important role in the development of acute pancreatitis.IL-6 is an early marker to assess the pancreatic necrosis. 5-Fu and octreotide are benefit in treatment of acute necrotizing pancreatitis.Inhibition of cytokines by 5-Fu and octreotide may be their another therapeutic mechanism for treatment of acute pancreatitis.