Effect and mechanism of Bafiomycin A1 on acute pancreatitis in mice

Objective To investigate the effect and mechanism of Bafiomycin A1 on acute pancreatitis in mice. Methods 60 BALB/c mice were randomly divided into control group, model group, low dose group and high dose group (15 mice in each group). Model group, low dose group and high dose group of mice by intraperitoneal injection of caerulein 50 g/kg, 1/h, a total of 7 times to establish the model of acute pancreatitis. Mice in low dose group and high dose group were intraperitoneally injected with 25 and 75 μg/kg Bafiomycin A1. Mice in the control group and model group were injected with equal volume of normal saline intraperitoneally. Mice in four groups were sacrificed in 24 h after treatment. Serum amylase in mice (AMY), inflammatory factor tumor necrosis factor-α (TNF-α) and interleukin (IL)-6 were analyzed by enzyme linked immunosorbent assay (ELISA). The mouse pancreatic lesions and score (Schmidt score) were analyzed by hematoxylin and eosin (HE) staining. autophagy substrate p62 and microtubule-associated protein 1 light chain 3 (LC3) were detected by Western blotting. The pancreatic tissue p62 were analyzed by immunofluorescence. Results Compared with the model group [(4 910.98±349.43) U/L, (109.43±10.43) pg/L, (329.16±20.91) pg/L, 9.43±3.98], the AMY, TNF-α, IL-6 and Schmidt scores of the low dose group [(3 109.13±301.44) U/L, (80.18±9.34) pg/L, (215.32±18.43) pg/L, 6.48±3.18] and the high dose group [(1 432.33±187.43) U/L, (45.19±8.14) pg/L, (153.22±12.63) pg/L, 3.14±1.02] significantly decreased (P=0.000). Compared with the low dose group, the AMY, TNF-α, IL-6 and Schmidt scores of the high dose group more significantly decreased. Compared with model group (0.15±0.06, 0.56±0.06), p62 and LC3 in pancreatic tissue of mice in low dose group (0.39±0.09, 0.75±0.09) and high dose group (0.61±0.07, 0.99±0.08) obviously enhanced (P=0.000). Compared with the low dose group, the accumulation of p62 and LC3 in the pancreatic tissue of the high dose group more obviously accumulated (P=0.000). Conclusion Bafiomycin A1 can significantly inhibit the level of autophagy in pancreatic tissue of mice with acute pancreatitis and play a protective role in pancreatic tissue. Key words: Acute pancreatitis; Autophagy; Bafiomycin A1; Inflammation