15-deoxy-delta 12,14-prostaglandin J2 prevents inflammatory response and endothelial cell damage in rats with acute obstructive cholangitis.
15-deoxy-delta 12,14-prostaglandin J2 prevents inflammatory response and endothelial cell damage in rats with acute obstructive cholangitis.
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DOI：
10.1152/ajpgi.00233.2009
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发表时间：
2010
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影响因子：
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通讯作者：
Katsutaka Watanabe;Y. Yokoyama;T. Kokuryo;K. Kawai;Tomomi Kitagawa;T. Seki;A. Nakagawa;M. Nagino
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文献类型：
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作者：
Katsutaka Watanabe;Y. Yokoyama;T. Kokuryo;K. Kawai;Tomomi Kitagawa;T. Seki;A. Nakagawa;M. Nagino
急性梗阻性胆管炎是一种常见病，死亡率高。过氧化物酶体增殖激活受体γ (PPARgamma)的配体，如15-脱氧- δ(12,14)-前列腺素J(2) (15D-PGJ(2))，已被提出作为一类新的抗炎化合物。本研究探讨15D-PGJ(2)对脂多糖（LPS）诱导的急性梗阻性胆管炎的影响。将大鼠随机分为5组：假手术（sham；单腹开腹）、假手术联合腹腔盐水输注（sham + saline）、假手术联合腹腔LPS输注（sham +LPS）、胆管结扎（BDL）联合胆管盐水输注（BDL+ saline）、BDL联合胆管LPS输注（BDL+LPS）。对血液样本、肝脏组织学、门静脉压、透明质酸清除率和肝脏炎症相关基因的表达进行生化分析。并将Sham+LPS组和BDL+LPS组分为两组（分别给予和不给予15D-PGJ(2)治疗），比较其生存率。与BDL+生理盐水组相比，BDL+LPS组血液样本生化指标、门静脉压、透明质酸清除率、肝脏炎症相关基因表达均显著升高，表明第一组肝损伤加重。然而，术前给予15D-PGJ(2)可显著改善这些结果。此外，BDL+LPS组给予15D-PGJ(2)可显著提高胆管炎建立后的生存率。这些结果清楚地表明，15D-PGJ(2)抑制急性梗阻性胆管炎的炎症反应和内皮细胞损伤，并可能有助于改善该病理结果。
Acute obstructive cholangitis is a common disease with a high mortality rate. Ligands for peroxisome proliferator-activated receptor-gamma (PPARgamma), such as 15-deoxy-Delta(12,14)-prostaglandin J(2) (15D-PGJ(2)), have been proposed as a new class of anti-inflammatory compounds. This study investigated the effect of 15D-PGJ(2) treatment on lipopolysaccharide (LPS)-induced acute obstructive cholangitis. The rats were randomly assigned to five groups: sham operation (Sham; simple laparotomy), sham operation with intraperitoneal saline infusion (Sham+Saline), sham operation with intraperitoneal LPS infusion (Sham+LPS), bile duct ligation (BDL) with saline infusion into the bile duct (BDL+Saline), and BDL with LPS infusion into the bile duct (BDL+LPS). Biochemical assays of blood samples, histology of the liver, portal venous pressure, hyaluronic acid clearance, and expression of inflammation-associated genes in the liver were evaluated. Furthermore, the Sham+LPS and the BDL+LPS group were divided into two groups (with and without 15D-PGJ(2) treatment), and their survival rates were compared. Biochemical assays of blood samples, portal venous pressure, hyaluronic acid clearance, and expression of inflammation-associated genes in the liver were all significantly higher in the BDL+LPS group compared with those in the BDL+Saline group, indicating the presence of increased liver damage in the first group. However, preoperative administration of 15D-PGJ(2) significantly improved these outcomes. Furthermore, the survival rate after establishment of cholangitis was significantly improved by the administration of 15D-PGJ(2) in the BDL+LPS group. These results clearly demonstrate that 15D-PGJ(2) inhibits the inflammatory response and endothelial cell damage seen in acute obstructive cholangitis and could contribute to improve the outcome of this pathology.