Dembiński Artur, Warzecha Zygmunt, Ceranowicz Piotr, Tomaszewska Romana, Dembiński Marcin, Pabiańczyk Małgorzata, Stachura Jerzy, Konturek Stanisław J
Department of Physiology, Jagiellonian University Medical School, 16 Grzegórzecka Street, 31-531 Cracow, Poland.
Eur J Pharmacol. 2003 Jul 25;473(2-3):207-16. doi: 10.1016/s0014-2999(03)01994-0.
In various organs, including heart, kidneys, brain, liver and stomach, preconditioning by brief exposure to ischemia protects the organ against damage evoked by subsequent severe ischemia. This study has been undertaken to check whether two brief ischemic periods protect the pancreas against severe ischemia/reperfusion-induced pancreatitis and, if so, what is the role of sensory and vagal nerves in this phenomenon. In male Wistar rats, the ischemic preconditioning of the pancreas was performed by clamping of celiac artery (2 x 5 min with 5 min interval). Thirty minutes after preconditioning or sham operation, the ischemia/reperfusion-induced pancreatitis was evoked by clamping of inferior splenic artery for 30 min using microvascular clips, followed by 1 h reperfusion. Sensory nerves ablation was induced 10 days before final experiments by capsaicin. Truncal vagotomy was performed 1 week before the experiment. Exposure to regular 30-min pancreatic ischemia followed by 1 h reperfusion led to the development of acute hemorrhagic pancreatitis. Ischemic preconditioning, applied prior to induction of pancreatitis, caused the reduction in plasma lipase, plasma interleukin-1beta and histological signs of pancreatic damage, as well as attenuated the reduction in pancreatic blood flow and DNA synthesis. Ablation of sensory nerves by capsaicin caused an aggravation of ischemia/reperfusion-induced pancreatic damage and attenuated a protective effect of ischemic preconditioning. Noxious effect of sensory nerves ablation on the pancreas was accompanied by the reduction in pancreatic blood flow and an increase in plasma interleukin-1beta. Similar but less pronounced deleterious effect on the pancreas was observed after vagotomy. We conclude that: (1) pancreatic ischemic preconditioning reduces the severity of ischemia/reperfusion-induced pancreatitis; (2) this effect seems to be related, at least in part, to the improvement of pancreatic blood flow and the reduction in the release of proinflammatory interleukin-1beta; (3) sensory and vagal nerves are involved in protective effect of ischemic preconditioning against pancreatic damage.
在包括心脏、肾脏、大脑、肝脏和胃在内的各种器官中，短暂暴露于缺血状态进行预处理可保护器官免受随后严重缺血所引发的损伤。本研究旨在检验两个短暂缺血期是否能保护胰腺免受严重缺血/再灌注诱导的胰腺炎，若能保护，感觉神经和迷走神经在此现象中起何种作用。在雄性Wistar大鼠中，通过夹闭腹腔动脉（2次，每次5分钟，间隔5分钟）对胰腺进行缺血预处理。预处理或假手术后30分钟，使用微血管夹夹闭脾下动脉30分钟，随后再灌注1小时，从而诱发缺血/再灌注诱导的胰腺炎。在最终实验前10天，用辣椒素诱导感觉神经消融。在实验前1周进行迷走神经干切断术。暴露于常规30分钟的胰腺缺血再灌注1小时会导致急性出血性胰腺炎的发生。在诱导胰腺炎之前进行缺血预处理，可使血浆脂肪酶、血浆白细胞介素-1β降低以及胰腺损伤的组织学征象减轻，同时减弱胰腺血流和DNA合成的降低。辣椒素消融感觉神经会加重缺血/再灌注诱导的胰腺损伤，并减弱缺血预处理的保护作用。感觉神经消融对胰腺的有害作用伴随着胰腺血流的减少和血浆白细胞介素-1β的增加。迷走神经切断术后观察到对胰腺有类似但不太明显的有害作用。我们得出以下结论：（1）胰腺缺血预处理可降低缺血/再灌注诱导的胰腺炎的严重程度；（2）这种作用似乎至少部分与胰腺血流的改善以及促炎白细胞介素-1β释放的减少有关；（3）感觉神经和迷走神经参与了缺血预处理对胰腺损伤的保护作用。
