Dembiński A, Warzecha Z, Ceranowicz P, Dembiński M, Cieszkowski J, Pawlik W W, Tomaszewska R, Konturek S J, Konturek P C
Department of Physiology, Jagiellonian University Medical College, Kraków, Poland.
J Physiol Pharmacol. 2006 Mar;57(1):39-58.
Ischemic preconditioning has been shown to protect several organs from ischemia/reperfusion-induced injury. In the pancreas, protective effect of ischemic preconditioning has been shown against pancreatitis evoked by ischemia/reperfusion, as well as by caerulein. However, the effect of ischemic preconditioning on the course of acute pancreatic is unclear. The aim of our study was to evaluate the influence of ischemic preconditioning on pancreatic regeneration and pancreatic presence of platelet-derived growth factor-A (PDGF-A) and vascular endothelial growth factor (VEGF) in the course of ischemia/reperfusion-induced pancreatitis.
In male Wistar rats, ischemic preconditioning of the pancreas was performed by short-term clamping of celiac artery (twice for 5 min with 5 min interval). Acute pancreatitis was induced by clamping of inferior splenic artery for 30 min followed by reperfusion. Rats were sacrificed 1, 5, 12 h or 1, 2, 3, 5, 7, 9 and 21 days after the start of reperfusion. Severity of acute pancreatitis and pancreatic regeneration were determined by biochemical and morphological examination, expression of growth factors was determined by immunohistochemical analysis.
In ischemia/reperfusion-induced pancreatitis, the pancreatic damage reached the maximal range between the first and second day of reperfusion, and was followed by subsequent pancreatic regeneration. Ischemic preconditioning alone caused mild passing pancreatic damage and an increase in plasma concentration of pro-inflammatory interleukin-1 and anti-inflammatory interleukin-10. Ischemic preconditioning applied before ischemia/reperfusion-induced pancreatitis reduced morphological and biochemical signs of the pancreatitis-evoked pancreatic damage and accelerated pancreatic regeneration. This effect was associated with improvement of pancreatic blood flow. Ischemic preconditioning, ischemia/reperfusion-induced pancreatitis and their combination increased the presence of VEGF in acinar and islet cells, and immunostaining for PDGF-A in blood vessels. This effect was maximally pronounced after combination of ischemic preconditioning plus pancreatitis and occurred earlier than after pancreatitis alone.
Ischemic preconditioning reduces pancreatic damage and accelerates pancreatic healing in the course of ischemia/reperfusion-induced pancreatitis. This effect is associated with the increase in plasma concentration of anti-inflammatory interleukin-10, improvement of pancreatic blood flow and alteration of pancreatic immunohistochemical expression of PDGF-A and VEGF.
缺血预处理已被证明可保护多个器官免受缺血/再灌注诱导的损伤。在胰腺中，缺血预处理已显示出对缺血/再灌注以及蛙皮素诱发的胰腺炎具有保护作用。然而，缺血预处理对急性胰腺炎病程的影响尚不清楚。我们研究的目的是评估缺血预处理对缺血/再灌注诱导的胰腺炎病程中胰腺再生以及血小板衍生生长因子-A（PDGF-A）和血管内皮生长因子（VEGF）在胰腺中的表达的影响。
在雄性Wistar大鼠中，通过短期夹闭腹腔动脉（两次，每次5分钟，间隔5分钟）对胰腺进行缺血预处理。通过夹闭脾下动脉30分钟然后再灌注诱导急性胰腺炎。在再灌注开始后1、5、12小时或1、2、3、5、7、9和21天处死大鼠。通过生化和形态学检查确定急性胰腺炎的严重程度和胰腺再生情况，通过免疫组织化学分析确定生长因子的表达。
在缺血/再灌注诱导的胰腺炎中，胰腺损伤在再灌注的第一天到第二天达到最大程度，随后是胰腺再生。单独的缺血预处理导致轻度短暂的胰腺损伤以及促炎白细胞介素-1和抗炎白细胞介素-10血浆浓度升高。在缺血/再灌注诱导的胰腺炎之前进行缺血预处理可减轻胰腺炎诱发的胰腺损伤的形态学和生化指标，并加速胰腺再生。这种作用与胰腺血流的改善有关。缺血预处理、缺血/再灌注诱导的胰腺炎及其联合作用增加了腺泡和胰岛细胞中VEGF的表达以及血管中PDGF-A的免疫染色。这种作用在缺血预处理加胰腺炎联合后最为明显，且比单独的胰腺炎发生得更早。
缺血预处理可减轻缺血/再灌注诱导的胰腺炎病程中的胰腺损伤并加速胰腺愈合。这种作用与抗炎白细胞介素-10血浆浓度升高、胰腺血流改善以及胰腺中PDGF-A和VEGF免疫组织化学表达的改变有关。
