摘要
背景：5-脂氧合酶（5-LOX）是将花生四烯酸、亚油酸和其他多不饱和脂肪酸转变为具有生物活性的代谢产物如自三烯类的限速酶，从而影响细胞信号转导、结构和代谢。然而关于其在重症急性胰腺炎（SAP）中作用的研究尚少。目的：研究选择性5-LOX抑制剂齐留通对急性坏死性胰腺炎（ANP）大鼠中性粒细胞活化的作用。方法：将54只Sprague—Dawley大鼠随机分为假手术组、ANP组和齐留通组。以5％牛磺胆酸钠胰胆管逆行注射诱导ANP模型。各组大鼠分别于6h、12h和24h处死。行胰腺组织病理学评分，以酶联免疫吸附测定（ELISA）检测血清可溶性细胞间黏附分子-1（sICAM-1）、可溶性E-选择素（sE-选择素）和可溶性P-选择素（sP-选择素）水平．以免疫组化染色检测胰腺缉织ICAM-1、E-选择素和P-选择素的表达，常规方法检测胰腺组织髓过氧化物酶（MPO）活性和血清淀粉酶水平。结果：与假手术组相比，ANP组同时间点胰腺组织病理学评分、廊清sICAM-1、sE-选择素和sP-选择素水平、胰腺组织ICAM-1、E-选择素和P-选择素表达以及胰腺组织MPO活性和血清淀粉酶水平均显著增高（P＜0．05）。经齐留通预处理后，除外6h组的组织病理学评分，上述各项指标均较同时间点ANP组显著降低（P＜0．05）。结论：选择性5-LOX抑制剂齐留通能通过抑制中性粒细胞活化而有助于减轻ANP大鼠胰腺组织学损伤。
Background：5-1ipoxygenase （5-LOX） is a rate-limiting enzyme in the catalysis of arachidonie acid, linoleie aeid and other polyunsaturated fatty acid into some bioaetive metabolic products, such as leukotrienes, thereby affeeting the eellular signal transduetion, structure and metabolism. However, few studies have been focused on the role of 5-LOX in severe acute pancreatitis （SAP）. Aims： To investigate the effect of zileuton, a selective inhibitor of 5-LOX, on activation of neutrophils in rats with acute necrotizing pancreatitis （ANP）. Methods： Fifty-four Sprague-Dawley rats were randomly divided into 3 groups： sham-operated group, ANP group and zileuton-treated group. The model of ANP was induced by retrograde injection of 5% sodium taurocholate into pancreatobiliary duct. The animals were sacrificed at the 6th, 12th and 24th hour. The histopathologic score of pancreatic tissue was evaluated. The serum levels of soluble intercellular adhesion molecule （sICAM）-1, soluble E-selectin （sE-selectin） and soluble P-selectin （sP-selectin） were determined by enzymelinked immunosorbent assay （ELISA）. The expressions of ICAM-1, E-selectin and P-selectin in pancreatic tissue were determined by immunohistochemistry. The activity of myeloperoxidase （MPO） in pancreatic tissue and serum level of amylase were determined. Results： Compared with sham-operated group, the histopathologic score of pancreatic tissue,the serum levels of sICAM-1, sE-selectin and sP-selectin, expressions of ICAM-1, E-selectin and P-selectin in pancreatic tissue, activity of MPO and serum level of amylase in ANP group at the same time point increased significantly （P〈0.05）. In zileuton-treated group, except the histopathologic score in 6-hour group, all the above-mentioned indices decreased significantly when compared with those in ANP group at the same time point （P〈0.05）. Conclusions： Zileuton, the selective inhibitor of 5-LOX, can mitigate the histological damage through inhibiting the activation of neutrophils in rats with ANP.
出处
《胃肠病学》
2009年第3期146-150,共5页
Chinese Journal of Gastroenterology
