The protective effects of Lipoxin A4 during the early phase of severe acute pancreatitis in rats
The protective effects of Lipoxin A4 during the early phase of severe acute pancreatitis in rats
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DOI：
10.3109/00365521.2010.525715
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发表时间：
2011-01
影响因子：
1.9
通讯作者：
Mengtao Zhou;Bi-cheng Chen;Hong-wei Sun;Z. Deng;R. Andersson;Qiyu Zhang
中科院分区：
文献类型：
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作者：
Mengtao Zhou;Bi-cheng Chen;Hong-wei Sun;Z. Deng;R. Andersson;Qiyu Zhang
抽象目标。本研究旨在探讨脂氧素A4类似物(LXA4)对大鼠急性胰腺炎早期的保护作用。材料和方法。用5%牛磺胆酸钠胰管内注射诱导重症急性胰腺炎(SAP)。LXA4组在注射5%牛磺胆酸钠后10min给予LXA4(0.1 mg/kg)，然后每8h给药一次，共3次。假手术组只在手术后才给车。分别于造模后4、12、24 h检测血浆淀粉酶活性、血清白介素1(IL-1)、白介素6(IL-6)和肿瘤坏死因子-α(肿瘤坏死因子-α)水平。采用免疫组织化学方法检测胰腺组织中细胞间黏附分子-1(ICAM-1)、核因子-κB p65的表达及肺组织中细胞间黏附分子-1的表达。结果。与SAP组比较，LXA4治疗组大鼠在各时间点的血清肿瘤坏死因子-α、IL-1和IL-6水平均显著降低(p<0.05)，而血浆淀粉酶活性仅在24 h时有显著差异。LXA4组胰腺指数和胰腺组织病理学评分均低于SAP组。免疫组织化学结果显示，LXA4可抑制胰腺组织中ICAM-1和NF-κB p65的表达，降低胰腺组织中ICAM-1在肺组织中的表达。结论。我们证明LXA4对实验性重症急性胰腺炎具有保护作用，这可能是通过抑制NF-κB信号通路从而减少促炎细胞因子的产生而实现的。
Abstract Objective. Our aim was to investigate the protective effects of a Lipoxin A4 analogue (LXA4) in the early phase of acute pancreatitis in rats. Materials and 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.