Inhibition of cathepsin B protects pancreatic acinar cells against apoptosis in early pancreatic trauma in rats

Abstract

Abstract Objectives: To observe the protective effect of cathepsin B inhibition against apoptosis of acinar cells in the early management of pancreatic contusion and laceration in rats, which would provide evidence of a potential early therapeutic for pancreatic contusion and laceration. Methods: Twenty-four rats were assigned to 2 groups: 1) Model (n = 12) with an induced pancreatic injury of severity I–II and 2) CA074-V (n = 12): an induced pancreatic injury, severity I–II treated with the cathepsin B inhibitor CA074-me (0.01 mg/g) by intravenous administration through the caudal vein at 5 minutes post model establishment. The mice in these two groups were further randomly divided into 4 subgroups containing 3 rats each that were sacrificed for quantitation of apoptosis, immunohistochemistry of cathepsin B, and serum amylase and lipase measurements at different time points after model establishment (0, 3, 6, and 12 hours). Results: The percentage of apoptotic pancreatic acinar cells collected from the injured tissues were much lower in the CA074-V group than the Model group at 3 hours [9.25 ± 3.94% vs. 64.76 ± 26.47%, P < 0.10] and 6 hours [14.71 ± 8.22% vs. 66.60 ± 13.54%, P < 0.10] post model establishment. The percentage of cathepsin B-positive pancreatic acinar cells were much lower in the CA074-V group than in the Model group at 3 hours [31.07 ± 12.02% vs. 69.16 ± 5.71%, P < 0.10], 6 hours [24.84 ± 0.93% vs. 47.06 ± 0.91%, P < 0.10], and 12 hours [28.33 ± 9.14% vs. 52.72 ± 1.25%, P < 0.10] post model establishment. Conclusions: Early cathepsin B inhibition effectively blocked acinar cell apoptosis in an experimental rat model of pancreatic contusion and laceration.