Key result
Regional arterial infusion with Aspirin-Triggered Lipoxin A4 significantly attenuated the severity of experimental severe acute pancreatitis in rats, reducing serum levels of pro-inflammatory cytokines (P<0.01).
Why the study?
Does regional arterial infusion with Aspirin-Triggered Lipoxin A4 attenuate experimental severe acute pancreatitis in rats?
Does regional arterial infusion with Aspirin-Triggered Lipoxin A4 attenuate experimental severe acute pancreatitis in rats?
p-value: p=<0.01
Regional arterial infusion with Aspirin-Triggered Lipoxin A4 attenuates the severity of experimental severe acute pancreatitis in rats by down-regulating the NF-κB signaling pathway and reducing pro-inflammatory cytokines.
Supports ATL A4 exploration in pancreatitis models; leaves open translation to human therapy.
OBJECTIVE: Investigate the therapeutic effect of regional arterial infusion (RAI) with Aspirin-Triggered Lipoxin A4 (ATL) in experimental severe acute pancreatitis (SAP) in rats. MATERIALS AND METHODS: SAP 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. RESULTS: ATL 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. CONCLUSIONS: We 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.
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Yang et al. (2014) studied Severe acute pancreatitis (n=42). Regional arterial infusion with Aspirin-Triggered Lipoxin A4 (ATL) vs. Physiological saline was evaluated on Serum levels of pro-inflammatory cytokines (TNF-a, IL-1b, IL-6) and pancreatic injury markers (p=<0.01). Regional arterial infusion with Aspirin-Triggered Lipoxin A4 significantly attenuated the severity of experimental severe acute pancreatitis in rats, reducing serum levels of pro-inflammatory cytokines (P<0.01).
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