Abstract
Purpose: To study the anti-inflammatory influence of dexmedetomidine (DEX) in mice with acute pancreatitis (AP), and to determine the underlying mechanism.Methods: A total of 75 healthy ICR male mice were randomly divided into control, mild acute pancreatitis (MAP), MAP+DEX, severe acute pancreatitis (SAP), and SAP+DEX groups, with 15 mice/group. Blood levels of inflammatory factors (TNF-α and IL-1β) and norepinephrine were assayed ineach group. Western blotting was used to assay the protein expressions of NLRP3 and norepinephrine transporter (NET) in the pancreatic tissue of each group.Results: The levels of inflammatory factors in the MAP+DEX group were markedly lower than those in the MAP group after 10 h of MAP induction (p < 0.01). Mice in MAP+DEX group had significantly lower expression of NLRP3 in pancreatic tissue, and significantly higher NET protein level, relative to the MAP mice. Following 10 h of SAP, concentrations of the inflammatory factors and the pancreatic expression of NLRP3 were lower in SAP+DEX-treated mice than in SAP mice, while NET protein was significantly higher in SAP mice (p < 0.01).Conclusion: DEX reduces the expressions of inflammation-related factors TNF-α and IL-1β, and inhibits inflammatory response in mice with AP via downregulation of NET protein expression via inhibition of NLRP3 and early sympathetic events.
 Keywords: Dexmedetomidine, NLRP3 inflammasome, Sympathetic nerve, Acute pancreatitis, Inflammatory response
Highlights
Acute pancreatitis (AP) is a hemorrhage, edema, or necrotizing inflammatory response caused by pancreatic enzyme digestion of pancreatic tissue due to a variety of reasons
Effect of DEX on concentrations of inflammatory factors TNF-α and IL-1β in AP mice while norepinephrine transporter (NET) protein concentration was markedly lower in severe acute pancreatitis (SAP)-treated mice (p < 0.01)
The results of ELISA showed that after 10 h of AP, the levels of serum inflammatory factors TNF-α and IL-1β in mild acute pancreatitis (MAP), SAP, MAP + DEX, and SAP + DEX groups were significantly higher than the corresponding levels in the control group (p < 0.01)
Summary
Acute pancreatitis (AP) is a hemorrhage, edema, or necrotizing inflammatory response caused by pancreatic enzyme digestion of pancreatic tissue due to a variety of reasons. Dexmedetomidine (DEX), a classical selective a2 receptor agonist, significantly reduces sympathetic nerve activity It has been widely used in sedation and analgesia in critically-ill patients. Studies have shown that DEX maintains hemodynamic stability in some patients with underlying cardiovascular disease during perioperative period. The present study was carried out to unravel the influence of DEX on the level of inflammatory response in mice with AP, and the underlying mechanisms. This was with a view to providing more clinical evidence for early prevention and treatment of patients with AP.
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