Mchanism by which IL-1Ra induces apoptosis of pancreatic acinar cells during pancreatitis in rats

Objective:To investigate the ability of interleukin-1 receptor antagonist to induces apoptosis of pancreatic acinar cells during experimental acute pancreatitis in rats.Methods:A toatal 72 rats were randomly divided into three groups(each with 24 rats) :pancreatitis group,IL-1Ra interference group and control group.Under the pancreatic membrane injection of sodium deoxycholate was carried out to establish acute pancreatitis model in SD rats.Six rats were sacrificed at 1,2,6 and 12 h after the model was made.The apoptosis of pancreatic acinar cells was observed and apoptotic index was detected by terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling(TUNEL) method.The expression of apoptosis regulated gene Fas,FasL,Bax,Bcl-2 was detected by immunohistochemical technique. Results:Results from the TUNEL staining showed that the apoptotic index of pancreatic acinar cells in treated group at 1,2,6 and 12 hours after the induction of acute pancreatitis was significantly higher than ANP and control group at the same time(all P0.01).Immunohistochemical analysis showed that there were weak Fas and Bax staining cells and no Bcl-2 positive staining cells in normal pancreatic tissues.The positive rate of Bax protein in IL-1Ra treated group at 1,2,6 and 12 hours was significantly higher than those of ANP group respectively(all P0.01).The positive rate of Fas protein in IL-1Ra treat group at 1,2,6 and 12 hour was markedly higher than that of ANP group(all P0.01),while Bcl-2 remained unchanged in pancreatic acinar cells during acute pancreatitis,and the expression of FasL could only be detected in infiltrative inflammatory cells. Conclusion:During acute pancreatitis,induction of apoptosis in injured pancreatic acinar cells to reduce inflammatory response might be one of the mechanisms of IL-1Ra in treating acute pancreatitis in mice.The acinar cell apoptosis induced by IL-1Ra may be associated with activity regulation of Bax,Fas/ FasL system.