Saluja A K, Lu L, Yamaguchi Y, Hofbauer B, Rünzi M, Dawra R, Bhatia M, Steer M L
Department of Surgery, Beth Israel Hospital, Harvard Medical School, Boston, Massachusetts 02215, USA.
J Clin Invest. 1997 Feb 1;99(3):506-12. doi: 10.1172/JCI119186.
The mechanisms by which short-term ethanol administration alters pancreatic exocrine function are unknown. We have evaluated the effects of ethanol administration on pancreatic secretion of digestive enzymes. In our studies, anesthetized as well as conscious rats were given ethanol at a rate sufficient to cause the blood ethanol concentration to reach levels associated with clinical intoxication. Ethanol was administered over a 2-h period during which blood ethanol levels remained stably elevated. We report that intravenous administration of ethanol results in a transient increase in pancreatic amylase output and plasma cholecystokinin (CCK) levels. The ethanol-induced increase in amylase output can be completely inhibited by the CCK-A receptor antagonist L-364,718 and partially inhibited by the muscarinic cholinergic antagonist atropine. The ethanol-induced rise in amylase output can be completely prevented by instillation of trypsin into the duodenum or by lavage of the duodenum with saline during ethanol administration. Furthermore, the intraduodenal activity of a CCK-releasing factor is increased by infusion of ethanol. These studies indicate that administration of ethanol causes rat pancreatic exocrine secretion to increase. This phenomenon is mediated by a trypsin-sensitive CCK-releasing factor which is present within the duodenal lumen. These observations lead us to speculate that repeated CCK-mediated ethanol-induced stimulation of pancreatic digestive enzyme secretion may play a role in the events which link ethanol abuse to the development of pancreatic injury.
短期给予乙醇改变胰腺外分泌功能的机制尚不清楚。我们评估了给予乙醇对胰腺消化酶分泌的影响。在我们的研究中，给麻醉和清醒的大鼠以足以使血液乙醇浓度达到与临床中毒相关水平的速率给予乙醇。乙醇在2小时内给予，在此期间血液乙醇水平持续稳定升高。我们报告静脉注射乙醇会导致胰腺淀粉酶输出量和血浆胆囊收缩素（CCK）水平短暂增加。乙醇诱导的淀粉酶输出增加可被CCK-A受体拮抗剂L-364,718完全抑制，并被毒蕈碱胆碱能拮抗剂阿托品部分抑制。在乙醇给药期间，向十二指肠内注入胰蛋白酶或用盐水冲洗十二指肠可完全阻止乙醇诱导的淀粉酶输出增加。此外，输注乙醇会增加十二指肠内CCK释放因子的活性。这些研究表明，给予乙醇会导致大鼠胰腺外分泌增加。这种现象由十二指肠腔内存在的一种对胰蛋白酶敏感的CCK释放因子介导。这些观察结果使我们推测，CCK介导的乙醇诱导的胰腺消化酶分泌反复刺激可能在将乙醇滥用与胰腺损伤发展联系起来的事件中起作用。
