Zhou Mengtao, Chen Bicheng, Sun Hongwei, Deng Zhexian, Andersson Roland, Zhang Qiyu
Department of Surgery, The First Affiliated Hospital, Wenzhou Medical College, Wenzhou, China.
Scand J Gastroenterol. 2011 Feb;46(2):211-9. doi: 10.3109/00365521.2010.525715. Epub 2010 Oct 18.
Our aim was to investigate the protective effects of a Lipoxin A(4) analogue (LXA4) in the early phase of acute pancreatitis in rats.
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.
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).
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.
我们的目的是研究脂氧素A(4)类似物（LXA4）在大鼠急性胰腺炎早期阶段的保护作用。
通过向胰管注射5%牛磺胆酸钠诱导重症急性胰腺炎（SAP）。在注射5%牛磺胆酸钠10分钟后，用LXA4（0.1毫克/千克）治疗SAP大鼠，之后每8小时给药一次，共给药三次（LXA4组）。假手术组术后仅给予溶媒。在诱导SAP后4、12和24小时测量血浆淀粉酶活性、白细胞介素-1（IL-1）、IL-6和肿瘤坏死因子-α（TNF-α）的血清水平。评估胰腺指数和组织病理学观察结果，并通过免疫组织化学检测胰腺中细胞间黏附分子-1（ICAM-1）和NF-κB p65的表达以及肺中ICAM-1的表达。
在所有测量时间点，LXA4治疗的大鼠血清中TNF-α、IL-1和IL-6水平均较低（p<0.05），但与SAP组相比，仅在24小时时血浆淀粉酶活性有显著差异。与SAP组相比，LXA4组的胰腺指数和胰腺炎组织病理学评估得分较低。免疫组织化学显示，LXA4可减轻胰腺炎动物胰腺中ICAM-1和NF-κB p65的表达以及肺中ICAM-1的表达（p<0.05）。
我们证明LXA4在实验性SAP中具有保护作用，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来实现的。
