Abstract
ObjectiveInvestigate the therapeutic effect of regional arterial infusion (RAI) with Aspirin-Triggered Lipoxin A4 (ATL) in experimental severe acute pancreatitis (SAP) in rats.Materials and MethodsSAP was induced by injection of 5% sodium taurocholate into the pancreatic duct. Rats with SAP were treated with ATL (the ATL group) or physiological saline (the SAP group) infused via the left gastric artery 30 min after injection of sodium taurocholate. The sham group was subjected to the same surgical procedure, though without induction of SAP. Serum levels of amylase, phospholipase A2 (PLA2), interleukin-1β (IL-1β), IL-6 and tumor necrosis factor-α (TNF-α) were measured at 12 and 24 h after induction of SAP. Ascitic fluid, the pancreatic index (wet weight ratio) and myeloperoxidase (MPO) levels in the pancreas were determined and histopathological findings were evaluated. The expression of intercellular adhesion molecule-1 (ICAM-1), platelet endothelial cell adhesion molecule-1 (PECAM-1), NF-κB p65, and heme oxygenase-1 (HO-1) in the pancreas were estimated by immunofluorescence and western blot, respectively.ResultsATL rats had lower serum levels of TNF-α, IL-1β, and IL-6 (P<0.01), PLA2 (P<0.05), and amylase levels (P<0.05) studied as compared with the SAP group. The pancreatic index in the ATL group decreased only at 24 h as compared with the SAP group (P<0.05). The histopathological findings and MPO levels in the pancreas significantly decreased in the ATL group as compared to the SAP group (P<0.05 and P<0.01, respectively). Immunofluorescence and western blot showed that ATL attenuated the expression of NF-κB p65, ICAM-1 and PECAM-1 in the pancreas, and increased the expression of HO-1 in SAP animals.ConclusionsWe demonstrated that RAI with ATL attenuated the severity of experimental SAP, maybe achieved by improving the expression of HO-1, and down-regulating the NF-κB signaling pathway, with decreased expression of ICAM-1 and PECAM-1 and reduced generation of pro-inflammatory cytokines.
Highlights
The importance of inflammatory cells, their activations, and the inflammatory cascades involved in severe pancreatitis (SAP) has been emphasized [1]
Immunofluorescence and western blot showed that ATL attenuated the expression of NF-kB p65, intercellular adhesion molecule-1 (ICAM-1) and platelet endothelial cell adhesion molecule-1 (PECAM-1) in the pancreas, and increased the expression of heme oxygenase-1 (HO-1) in severe acute pancreatitis (SAP) animals
We demonstrated that regional arterial infusion (RAI) with ATL attenuated the severity of experimental SAP, maybe achieved by improving the expression of HO-1, and down-regulating the NF-kB signaling pathway, with decreased expression of ICAM-1 and PECAM-1 and reduced generation of pro-inflammatory cytokines
Summary
The importance of inflammatory cells, their activations, and the inflammatory cascades involved in severe pancreatitis (SAP) has been emphasized [1]. The main factor regulating the concomitant course of disease during the early phase of SAP is the magnitude of the systemic inflammatory response syndrome (SIRS). Proinflammatory cytokines have been considered responsible for systemic manifestations and complications of SIRS in SAP [6]. Cytokines cause both local and distant upregulation of adhesion molecules that further trigger inflammatory cascades by enhancing leukocyte migration, complement activation, neutrophil degranulation, production of phospholipase A2 (PLA2), nitric oxide, and oxygen radicals [7]. Minimizing the inflammatory cytokine response in order to avoid excessive SIRS seems essential
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