Effects of Snake-Derived Phospholipase A2 Inhibitors on Acute Pancreatitis: In vitro and in vivo Characterization
Objective We aimed to investigate the effects of snake-derived phospholipase A2 inhibitor (PLA2) from Sinonatrix percarinata and Bungarus multicinctus on acute pancreatitis in vivo and in vitro and assess the mechanisms.Methods The levels of platelet-activating factor (PAF) and tumor necrosis factor (TNF)-α were detected by ELISA, and the characteristics of autophagy were detected by transmission electron microscopy and Western blotting (LC3, p62, and ATG5).Results In vitro experiments showed that PLA2 treatment caused obvious formation of autophagic bodies. By contrast, Sinonatrix and Bungarus peptides reduced the number of autophagic bodies. The concentrations of PAF and TNF-α, and the expressions of p62, autophagy-related 5 (ATG5), and microtubule-associated protein 1A/1B-light chain 3 (LC3)II/LC3I in the PLA2-treated group were significantly higher than in the control group (P<0.05). The concentrations of PAF and TNF-α, and the expressions of p62, ATG5, and LC3II/LC3I in the Sinonatrix or Bungarus peptide treatment groups were significantly lower than in the PLA2-treated cells (P<0.05). In the pancreatic tissue, autophagic bodies were observed in the model group; autophagic bodies were remarkably reduced in Sinonatrix or Bungarus peptide-treated groups compared with the model group. In vivo experiments also showed that the levels of PAF and TNF-α, and the expressions of p62, ATG5, and LC3II/LC3I were significantly higher in the model group than in the control group (P<0.05). The levels of PAF and TNF-α in the model group, and the expressions of p62, ATG5, and LC3II/LC3I in Sinonatrix or Bungarus peptide-treated groups were significantly lower than in the model group (P<0.05).Conclusion Sinonatrix or Bungarus peptide could ameliorate the features of acute pancreatitis, likely through regulating autophagy.
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