Department of Physiology, Faculty of Medicine, Jagiellonian University Medical College, 31-531 Cracow, Poland.
Department of Anatomy, Faculty of Medicine, Jagiellonian University Medical College, 31-034 Cracow, Poland.
Molecules. 2020 May 27;25(11):2493. doi: 10.3390/molecules25112493.
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 µg/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 µg/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-1β and plasma level of D-dimer. In contrast, pretreatment with warfarin given at a dose of 270 µg/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.
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、白细胞滚动、黏附和迁移到胰腺组织以及凝血激活。先前的研究表明，肝素或乙酰水杨酸预处理可抑制 AP 的发展。本研究旨在检查华法林（一种口服维生素 K 拮抗剂）预处理对大鼠缺血/再灌注诱导的 AP 发展的影响。AP 通过胰腺缺血后再灌注诱导。华法林（90、180 或 270 µg/kg/剂量）或载体每天经胃内给药一次，共 7 天，然后诱导 AP。华法林对 AP 严重程度的影响在胰腺再灌注后 6 小时进行评估。评估包括组织学、功能和生化分析。以 90 或 180 µg/kg/剂量给予华法林预处理会增加国际标准化比值并减轻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。这些作用伴随着胰腺血流量的改善和血清淀粉酶、脂肪酶、促炎白细胞介素-1β和血浆 D-二聚体水平的降低。相比之下，以 270 µg/kg/剂量给予华法林预处理会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后再灌注诱导的 AP 的发展。
