Breviscapine attenuates acute pancreatitis by inhibiting expression of PKCα and NF-κB in pancreas

Abstract

Aim: To study the effect of breviscapine (Bre) on activity of protein kinase Cα (PKCα) and nuclear factor (NF)-κB in pancreas, and the mechanism of Bre attenuating acute pancreatitis (AP).

Methods: One hundred and eight rats were randomly divided into acute necrotizing pancreatitis (ANP) group, Bre group (ANP + Bre group) and sham operation (SO) group, 36 rats in each group. ANP model was induced by a retrograde injection of 4% sodium deoxycholate into the bilio-pancreatic duct. Fifteen minutes after the ANP model was induced, the rats in Bre group were intraperitoneally injected with Bre (0.4 mg/100 g body weight or 0.1 mL/100 g body weight). Survival time and mortality of rats were calculated. Serum amylase and malondialdehyde levels were measured, volume of ascites was recorded and morphology of pancreas and lung was evaluated at 1, 5 and 10 h, after the ANP model was induced, respectively. Expressions of PKCα and subunit p65 of NF-κB in pancreas were detected by immunohistochemistry and Western blotting.

Results: The life span of rats was longer and the mortality was lower in Bre group than in ANP group 13.51 ± 5.46 vs. 25.36 ± 8.11 (P < 0.05). The amylase and MDA levels as well as the volume of ascites were lower and the pathological changes in pancreas and lung were less in Bre group than ANP group (P < 0.05), indicating that the pancreatitis is less severe in Bre group than ANP group. The activation of PKCα and NF-κB p65 in pancreas was induced rapidly and reached their peak at 1 h or 5 h after ANP, but their activity in Bre group was significantly inhibited.

Conclusion: Bre exerts its therapeutic effect on AP by inhibiting the activation of PKCα and NF-κB p65 in pancreas.

Keywords: Acute pancreatitis; Breviscapine; Nuclear factor-κB; Protein kinase Cα; Rat.

Figure 1

Effect of breviscapine on mortality (A), ascites volume (B) and amylase activity (C), morphological change (D), morphological score (E), and malondialdehyde level (F) in rats with acute pancreatitis. ^aP < 0.05, ^bP< 0.01 vs SO group; ^cP < 0.05, ^dP < 0.01 vs ANP group. Bre: Breviscapine; SO: Sham operation; ANP: Acute necrotizing pancreatitis; MDA: Malondialdehyde.

Figure 2

Immunohistochemical analysis showing expression of protein kinase C alpha (PKCα) (A) and nuclear factor (NF)-κB P65 (B) in cytoplasm, membrane or nuclei of acini and inflammatory cells in pancreas, and western blotting showing the expression level of PKCα and NF-κB P65 in breviscapine and acute necrotizing pancreatitis groups at different time points (C). Bre: Breviscapine; SO: Sham operation; ANP: Acute necrotizing pancreatitis.