Activation Of NF-κB And Acinar Cell Apoptosis In Hyperlipidemic Rats With Severe Acute Pancreatitis

Objective:To investigate the effect of hyperlipidemia(HL) on severe acute pancreatitis(SAP) as well as the roles of activation of nuclear factor kappa B(NF-κB) and pancreatic acinar cell apoptosis in it.Methods:50 male SD rats were assigned randomly into 4 groups: control group with 10 rats,feeding balanced diet for 2 weeks then giving sham operations;HL group with 10 rats,giving stomach feeding with fat milk for 2 weeks to establish HL models then giving sham operations;SAP group with 15 rats,feeding balaned diet for the same time then injecting sodium taurocholate through puncturing the pancreatic duct to establish SAP models;HAP group with 15 rats, establishing HL models then making SAP models. Observeing their growing situation and weight changes during the time.All rats were killed at 6th hour after operations,blood was obtained for determination of serum triglyceride(TG) and cholesterol(CH) and amylase(AMS). Pancreatic tissues were prepared for routine light microscopy, using hematoxylin and eosin (HE) staining,and to evaluate the degree of tissue damage according to the Grewal,s method. The expressions of NF-κBp65 and Fas/FasL protein were detected by immunohistochemical method,and the apoptosis in pancreatic acinar cell was detected by TdT-mediated X-dUTP nick end labeling(TUNEL).Results:The weight of four groups was not significantly different.Total 50 rats entered final analysis:1. Serum levels of TG and CH and AMS:the serum levels of TG in HL and SAP groups were both higher than in the control group(P<0.01),and the serum level of CH in HL group was also higher than in the control group(P<0.01).The serum level of AMS in SAP group was higher than both in the control group and the HAP group(P<0.01).2.Pathologic score: the inflammation score in HL group was higher than in the control group(P<0.01),and both in the SAP and HAP groups,the oedema, necrosis,bleeding and inflammation scores were all higher than in the control group(P<0.01),moreover only the necrosis score in HAP group was higher than in the SAP group(P<0.05).3. NF-κBp65 expression: the expression level of active NF-κBp65 in pancreas in the HL group was higher than in the control group(P<0.05),but the expression extent in the two groups was not significant difference.The expression levels and extent of NF-κBp65 in SAP and HAP groups were both higher than in the control group(P<0.05), as well as they were higher in the HAP group than in the SAP group(P<0.05).4. Apoptosis index(AI) in pancreatic acinar cell:the AI of pancreatic acinar cells in HL and SAP groups was both higher than in the control group(P<0.05),and the AI in HAP group was lower than in the SAP group(P<0.05).5.Fas and FasL proteins expression:the expressions of Fas and FasL proteins in HL and SAP groups were both higher than in the control group(P<0.05),however in the HAP group they were both lower than in the SAP group(P<0.05).Conclusion:The activation of NF-κB is enhanced in the hyperlipidemic rats,that can produces the light inflammation in their pancreas,and their apoptosis index of pancreatic acinar cells as well as the expressions of Fas/FasL proteins are higher than normal rats. Moreover,the activation of NF-κB is also enhanced in the hyperlipidemic rats when they with SAP than the normal rats which are with SAP too, howerve their apoptosis index of pancreatic acinar cells as well as the expression levels of Fas/FasL proteins are lower,so the necrosis in their pancreas is severe .Therefor,to lower the blood fat level , and the inhibation of activation of NF-κB as well as to control the impaired pancreatic acinar cells death by the way of apoptosis may function as the feasible therapy strategies in hyperlipidemic patients who are with SAP.