[Protective effects and possible mechanism of lipoxin A(4) analogue in rats with acute pancreatitis].
OBJECTIVE
To explore the protective effects and possible mechanism of lipoxin A(4)-methyl ester (LXA(4)-ME) in rats with acute pancreatitis (AP).


METHODS
A total of 120 male SD rats were randomly divided into 3 groups: Sham operation (n = 40), AP (n = 40) and LXA(4)-ME (n = 40). Sham operation group received normal saline after sham operation. AP was induced by a retrograde infusion of 5% sodium taurocholate into pancreatobiliary duct. AP group received normal saline after modeling. In the LXA(4)-ME group, LXA(4)-ME was administered (87.5 µg/kg) intravenously after the onset of AP. The rats were sacrificed at 12 h and 24 h post-induction. Their serum levels of amylase were detected. The amount of ascites was calculated and histological changes of pancreas were observed. The activities of myeloperoxidase (MPO) and levels of malonaldehyde (MDA) in pancreas were determined. The mRNA levels of tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-10, intercellular adhesion molecule (ICAM-1), E-selectin and nuclear factor (NF)-κB p65 in pancreas were measured by reverse transcription-polymerase chain reaction (RT-PCR). The expression of NF-κB p65 protein was also measured by immunohistochemistry.


RESULTS
Compared with the AP group, the pathological scores of the LXA(4)-ME group improved (12 h: 8.7 ± 1.3 vs 11.3 ± 1.5, 24 h: 7.8 ± 1.1 vs 11.7 ± 0.8) and the amount of ascites was lower(12 h: (6.88 ± 1.23) ml vs (12.32 ± 1.94) ml, 24 h: (6.53 ± 0.91) ml vs (14.15 ± 1.68) ml, all P < 0.01). The serum levels of amylase in the LXA(4)-ME group were significantly lower than those in the AP group respectively at 12 h and 24 h post-operation (all P < 0.01). The activity of MPO and the level of MDA in pancreas in the LXA(4)-ME group were significantly lower than those in the AP group (all P < 0.01). The pancreatic expressions of TNF-α mRNA, IL-1β mRNA, ICAM-1 mRNA, E-selectin mRNA and NF-κB p65 mRNA at 12 h and 24 h decreased in the LXA(4)-ME group versus the AP group at the corresponding time points (all P < 0.01)while the expression of IL-10 mRNA increased versus the AP group at the corresponding time points (all P < 0.01). Compared with that in the AP group, the pancreatic expression of NF-κB p65 protein decreased in the LXA(4)-ME group (12 h: 24.8% ± 3.0% vs 45.3% ± 3.4%, 24 h: 31.6% ± 3.0% vs 48.1% ± 4.6%, both P < 0.01).


CONCLUSIONS
LXA(4)-ME exerts protective effects in AP rats. And its mechanism may be due to the suppression of NF-κB activation.
Department of Gastroenterology, Second Affiliated Hospital, Soochow University, Suzhou 215004, China.
Chun-hua
CH
Zhou
Shao-feng
SF
Wang
Chuang-ying
CY
Hu
Hua-mei
HM
Fang
Xiao-yan
XY
Zhu
Ling-yun
LY
Li
Ming-jie
MJ
Qian
Duan-min
DM
Hu
Yong
Y
Yang
D000208:Acute Disease; D000818:Animals; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D044045:Lipoxins / Q000494:pharmacology* / Q000627:therapeutic use*; D008297:Male; D016328:NF-kappa B / Q000378:metabolism; D010195:Pancreatitis / Q000188:drug therapy* / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D044045:Lipoxins; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; C040527:lipoxin A4; D018799:Intercellular Adhesion Molecule-1