| Part1 The effect of sivelestat against pancreatic injury after severe acute pancreatitis in ratsObjectivesTo study the effect of treatment with sivelestat on the pancreatic injury in rats with severe acute pancreatitis, by observing the levels of serum NE, IL-6 and the levels of blood platelet,HCT and the pathology of pancreas.MethodsFifty-four SD rats were randomly divided into three groups:control group (group A), severe acute pancreatitis group (group B) and treatment group with sivelestat (group C). Each group was divided into 3h, 6h and 12h subgroups (n=6 in each subgroup). SAP was induced by retrograde injection of 3.5% sodium taurocholate into biliopancreatic duct. Sivelestat (5mg/100g/h) was instilled continuously into right jugular vein with infusion pump in the group C. Rats of group A were only operated with a celiotomy, normal saline (0.5ml/100g/h) was instilled in the group A and B. Six rats from each subgroup were killed, then the correlated indexes were evaluated at 3h, 6h,and 12h after the model had been developed. The level of serum amylase and the levels of blood platelet,HCT were measured by biochemical analyzer. The levels of NE in serum, IL-6 in serum were measured by ELISA. The wet-to-dry (W/D) weight ratio of pancreas were measured. The weight of ascitic fluid in abdominal cavity was measured. Part of pancreatic tissue was changed by HE staining, then the morphologic changes were evaluated.Results1. Pancreatic tissue:1.1.Normal pancreatic tissue was observed in group A. Cloudy bloody scites, mesenteric saponification spots, pancreatic edema and pancreatic local or lamellar necrosis were observed in group B and group C. Acinar cell edema, necrosis, interstitial haemorrhage and neutrophil and monocyte infiltration were observed in the pancreatic tissue of group B and group C by the means of microscopic examination. The changes of morphology were obviously lower in group C at three time points.1.2.In group B, pathological injury was gradually aggratated with time prolonged. The scores of pathological changes of pancreas in group B were significantly higher than those of group A at three time points (P<0.05). There was a significant difference between group C and group B at three time points (P<0.05).1.3.W/D weight ratio of pancreas in group B were found significantly higher than those in group A at three time points (P<0.05). In group C, W/D weight ratio of pancreas were significantly lower compared with those in group B at 6h and 12h (P<0.05).2.There was no ascitic fluid in abdominal cavity in group A. The weight of ascitic fluid in group C were significantly lower compared with those in group B at three time points (P<0.05).3.In group B, the levels of the levelas of blood platelet,HCT were obviously increased with time was prolonged (P<0.05). At three time points, both the levels of platelet and HCT in group B were significantly higher than those in group A (P<0.05). In group C, it was not significantly lower compared with those in group B at three time points (P>0.05).4.At three time points, the levels of serum amylase in group B were obviously higher than those of group A (P<0.05) and the levels of serum amylase were significant difference between group B and C only at 12h (P<0.05).5.In group B, the levels of serum NE and serum IL-6 were obviously increased with time was prolonged (P<0.05). At three time points, the levels of NE in serum in group B were significantly higher than those in group A (P<0.05). In group C, it was significantly lower compared with those in group B at three time points (P<0.05). The levels of IL-6 in serum in group B were significantly higher than those in group A at three time points (P<0.05). In group C, the levels of IL-6 in serum were significantly lower compared with those in group B at three time points. The statistical difference was significant (P<0.05).6.In group B, the levels of pancreatic tissue bomogenate MPO were obviously increased with time was prolonged (P<0.05). At three time points, the the levels of pancreatic tissue bomogenate MPO in group B were significantly higher than those in group A (P<0.05). In group C, it was significantly lower compared with those in group B at three time points (P<0.05).7.There was a positive correlation between the levels of NE in serum and the scores of pathological changes of pancreas (r=0.779, P<0.05). There was a positive correlation between the levels of IL-6 in serum and the scores of pathological changes of pancreas (r=0.745, P<0.05).Conclusions:1.The levels of IL-6 and NE in serum played an important role on determining severe degree of SAP.2.Neutrophil elastase appear to be involved in neutrophil accumulation and neutrophil-mediated pancreatic injury.The treatment with Sivelestat,a neutrophil elastase inhibitor,could markedly atteneuate pancreatic injury after Severe Acute Pancreatitis in Rats.Part II The Effect of Sivelestat against pancreatic injury after severe acute pancreatitis in ratsObjectivesTo study the role of Sivelestat in the hepatic injury in rats with severe acute pancreatitisMethodsFifty-four SD rats were randomly divided into three groups:Control group (group A), severe acute pancreatitis group (group B) and treatment group with Sivelestat (group C). Each group was divided into 3h, 6h and 12h subgroups (n=6 in each subgroup). SAP was induced by retrograde injection of 3.5% sodium taurocholate into biliopancreatic duct. Sivelestat (5mg/100g/h) was instilled continuously into right jugular vein with infusion pump in the group C. Rats of group A were only operated with a celiotomy, Normal saline (0.5ml/100g/h) was instilled in the group A and B. Six rats from each subgroup were killed, then the correlated indexes were evaluated at 3h, 6h, and 12h after the model had been developed. The level of serum AST and ALT were measured. The levels of SOD,MDA in hepatic tissue bomogenate were measured. The levels of IL-6 and NE in serum were measured by ELISA. Part of hepatic tissue was changed by HE staining.Results:1.Histopathological observation:Diffuse bleeding liver surface with focal necrosis, liver volume increased capsule tension,color grayred;Pathological changes of the rat liver: after Na-Tc treatment,inflammatory cell infiltration was noticed in hepatic tissue.Hepatic cells underwent a balloon-like degeneration.Boundary between individual hepatic cells became unclear;the cytoplasm appeared dot-like changes;inflammatory cell infiltration was found in portal area.2.In group B,the levels of serum NE and serum IL-6 were obviously increased with time was prolonged (P<0.05). At three time points, the levels of NE in serum in group B were significantly higher than those in group A (P<0.05). In group C, it was significantly lower compared with those in group B at three time points (P<0.05). The levels of IL-6 in serum in group B were significantly higher than those in group A at three time points (P<0.05). In group C, the levels of IL-6 in serum were significantly lower compared with those in group B at three time points. The statistical difference was significant (P<0.05).3. Compared with group A,the levels of serum AST,ALT and the levels of liver tissue bomogenate MDA were significantly increased in the group B (P<0.05). In group C, it was significantly lower compared with those in group B at three time points (P<0.05). The levels of liver tissue bomogenate SOD were significantly reduced in the group B (P<0.05).In group C, it was significantly higher compared with those in group B at three time points (P<0.05).Conclusion:1.The levels of serum NE,IL-6 and OFR were significantly increased which play an important role in the pathogenesis of SAP with liver damage.2.The treatment with Sivelestat,a elastase inhibitor,could markedly atteneuate hepatic injury in SAP enhancing the oxygen free radical scavenging capacity and inhibit neutrophil accumulation which reduce the level of LI-6. |
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