The protective effects of Lipoxin A4 during the early phase of severe acute pancreatitis in rats.
OBJECTIVE
Our aim was to investigate the protective effects of a Lipoxin A(4) analogue (LXA4) in the early phase of acute pancreatitis in rats.


METHODS
Severe acute pancreatitis (SAP) was induced by injection of 5% sodium taurocholate into the pancreatic duct. Rats with SAP were treated with LXA4 (0.1 mg/kg), 10 min after the 5% sodium taurocholate injection, after which LXA4 was administrated every 8 hours, three times (LXA4 group). The sham group was only given the vehicle after operation. Plasma amylase activity, serum levels of interleukin-1 (IL-1), IL-6, and tumor necrosis factor-α (TNF-α) were measured at 4, 12, and 24 h after induction of SAP. The pancreatic index and histopathologic observations were evaluated and the expression of intercellular adhesion molecule-1 (ICAM-1) and NF-κB p65 in the pancreas, and the expression of ICAM-1 in the lungs were detected by immunohistochemistry.


RESULTS
LXA4 treated rats had lower serum levels of TNF-α, IL-1, and IL-6 at all time points measured (p < 0.05), but significantly differed in plasma amylase activity only at 24 h as compared with the SAP group. The pancreatic index and the scores of pancreatitic histopathologic evaluations were lower in the LXA4 group as compared to the SAP group. Immunohistochemistry showed that LXA4 attenuated the expression of ICAM-1 and NF-κB p65 in the pancreas, as well as the expression of ICAM-1 in the lungs in animals with pancreatitis (p < 0.05).


CONCLUSIONS
We demonstrate that LXA4 has protective effects in experimental SAP, which may be achieved by inhibiting the NF-κB signalling pathway, thereby reducing the production of proinflammatory cytokines.
Department of Surgery, The First Affiliated Hospital, Wenzhou Medical College, Wenzhou, China.
Mengtao
M
Zhou
Bicheng
B
Chen
Hongwei
H
Sun
Zhexian
Z
Deng
Roland
R
Andersson
Qiyu
Q
Zhang
D000681:Amylases / Q000097:blood; D000818:Animals; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D007375:Interleukin-1 / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D044045:Lipoxins / Q000008:administration & dosage / Q000627:therapeutic use*; D008168:Lung / Q000378:metabolism; D055370:Lung Injury / Q000517:prevention & control*; D008297:Male; D016328:NF-kappa B / Q000378:metabolism; D010195:Pancreatitis / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction; D018746:Systemic Inflammatory Response Syndrome / Q000517:prevention & control*; D013656:Taurocholic Acid; D051996:Transcription Factor RelA / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
D007375:Interleukin-1; D015850:Interleukin-6; D044045:Lipoxins; D016328:NF-kappa B; D051996:Transcription Factor RelA; D014409:Tumor Necrosis Factor-alpha; C040527:lipoxin A4; D018799:Intercellular Adhesion Molecule-1; D013656:Taurocholic Acid; D000681:Amylases