Pretreatment with Warfarin Attenuates the Development of Ischemia/Reperfusion-Induced Acute Pancreatitis in Rats
Pretreatment with Warfarin Attenuates the Development of Ischemia/Reperfusion-Induced Acute Pancreatitis in Rats
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DOI：
10.3390/molecules25112493
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发表时间：
2020-06-01
期刊：
影响因子：
4.6
通讯作者：
Warzecha, Zygmunt
中科院分区：
文献类型：
--
作者：
Maduzia, Dawid;Ceranowicz, Piotr;Warzecha, Zygmunt
在急性胰腺炎（AP）中，胰腺损伤导致局部血管损伤，表现为内皮损伤和激活，血管通透性增加，白细胞向胰腺组织滚动、粘附和迁移，以及凝血激活。先前的研究表明，肝素或阿塞诺古豆醇预处理可抑制AP的发展。本研究的目的是检查口服维生素K拮抗剂华法林预处理对大鼠缺血/再灌注诱导AP发展的影响。胰脏缺血再灌注诱导AP。在诱导AP前7天，每天1次灌胃华法林（90、180或270 mu g/kg/剂量）或对照物。在胰腺再灌注6 h后评估华法林对AP严重程度的影响。评估包括组织学、功能和生化分析。90或180 μ g/kg/剂量的华法林预处理提高了国际标准化比率，减少了胰腺损伤的形态学迹象，如胰腺水肿、腺泡细胞空泡化、坏死和出血数量。这些影响伴随着胰腺血流的改善和血清淀粉酶、脂肪酶、促炎白细胞介素-1 β水平和血浆d -二聚体水平的降低。相比之下，270 μ g/kg/剂量的华法林预处理导致胰腺损伤的严重程度和AP的生化指标增加。此外，该剂量的华法林导致一些动物死亡。低剂量华法林预处理可抑制胰腺缺血再灌注所致AP的发展。
In acute pancreatitis (AP), pancreatic damage leads to local vascular injury, manifesting as endothelial damage and activation, increased vascular permeability, leukocyte rolling, sticking and transmigration to pancreatic tissue as well as activation of coagulation. Previous studies have shown that pretreatment with heparin or acenocoumarol inhibits the development of AP. The aim of the present study was to check the impact of pretreatment with warfarin, an oral vitamin K antagonist, on the development of ischemia/reperfusion-induced AP in rats. AP was induced by pancreatic ischemia followed by reperfusion of the gland. Warfarin (90, 180 or 270 mu g/kg/dose) or vehicle were administered intragastrically once a day for 7 days before induction of AP. The effect of warfarin on the severity of AP was assessed 6 h after pancreatic reperfusion. The assessment included histological, functional, and biochemical analyses. Pretreatment with warfarin given at a dose of 90 or 180 mu g/kg/dose increased the international normalized ratio and reduced morphological signs of pancreatic damage such as pancreatic edema, vacuolization of acinar cells, necrosis and the number of hemorrhages. These effects were accompanied by an improvement of pancreatic blood flow and a decrease in serum level amylase, lipase, pro-inflammatory interleukin-1 beta and plasma level of D-dimer. In contrast, pretreatment with warfarin given at a dose of 270 mu g/kg/dose led to an increase in severity of pancreatic damage and biochemical indicators of AP. In addition, this dose of warfarin resulted in deaths in some animals. Pretreatment with low doses of warfarin inhibits the development of AP induced by pancreatic ischemia followed by reperfusion.