Objective: This study aimed to investigate the role of glucose regulated protein 78 (GRP-78) in the apoptosis of neutrophils in rats with severe acute pancreatitis.
Methods: A total of 54 SD male rats were randomly assigned into 2 groups: sham group (n=24) and pancreatitis group (n=30). Severe acute pancreatitis was induced by retrograde cholangiopancreatography injection of sodium taurocholate. Rats were sacrified at 3 h, 6 h and 12 h after injection. In control group, rats received laparotomy, but the pancreates remained intact. The serum amylase was detected at different time points, and flow cytometry was done to detect the apoptosis of neutrophils. Proteins were extracted from neutrophils and subjected to detection of GRP78 and Mcl-1 expression by Western blot assay. HE staining was performed for pathological scoring of the pancreas.
Results: The serum amylase in pancreatitis group increased markedly when compared with control group (P<0.01). In SAP group, the serum amylase increased gradually over time (P<0.01). HE staining showed a lot of inflammatory cells and infiltration of red blood cells and the apoptosis rate of neutrophils reduced gradually (P<0.01). Western blot assay showed the protein expression of GRP-78 and Mcl-1 increased in neutrophils over time.
Conclusion: In rats with SAP, the apoptosis rate of neutrophils reduced over time, which may be associated to the stress induced expression of GRP78 and subsequent activation of Mcl-1 resulting in suppression of neutrphil apoptosis over time.
Keywords: 78 kDa glucose-regulated protein; cell apoptosis; myeloid cell leukemia 1; neutrophils; phosphatidylinositol kinase-3/serine-threonine protein kinase pathway; severe acute pancreatitis.