Harvey M H, Wedgwood K R, Reber H A
Department of Surgery, University of Missouri Health Sciences Center, Columbia.
Gastroenterology. 1987 Dec;93(6):1296-300. doi: 10.1016/0016-5085(87)90258-7.
We investigated the mechanisms by which 16,16-dimethyl prostaglandin E2 and histamine induced pancreatic hemorrhage in an experimental model of acute pancreatitis in cats. In normal animals, when large molecular weight dextran molecules were infused into the systematic circulation, they were recovered in secretin-stimulated pancreatic juice in low concentrations. Both 16,16-dimethyl prostaglandin E2 (in a dose that increased splenic artery blood flow and microvascular permeability) and histamine (in a dose that increased permeability only) increased the amount of dextran recovered in pancreatic juice. Isoproterenol, in a dose that produced the same increase in blood flow as 16,16-dimethyl prostaglandin E2 but which did not increase microvascular permeability, did not alter the amount of dextran recovered. This suggested that the increase in dextran output after 16,16-dimethyl prostaglandin E2 was primarily due to the increase in microvascular permeability caused by the drug. In other experiments, a combination of H1- and H2-receptor antagonists (mepyramine and cimetidine) protected against the development of pancreatic hemorrhage in both the prostaglandin- and histamine-treated animals. Indomethacin (a cyclooxygenase inhibitor) protected against the development of hemorrhage in the histamine-treated animals. Our results support the hypothesis that changes in microvascular permeability may be important in the pathogenesis of parenchymal hemorrhage in this model.
我们在猫急性胰腺炎实验模型中研究了16,16 - 二甲基前列腺素E2和组胺诱导胰腺出血的机制。在正常动物中，当将大分子右旋糖酐分子注入体循环时，它们会在促胰液素刺激的胰液中以低浓度被回收。16,16 - 二甲基前列腺素E2（剂量可增加脾动脉血流量和微血管通透性）和组胺（剂量仅增加通透性）均增加了胰液中回收的右旋糖酐量。异丙肾上腺素，剂量与16,16 - 二甲基前列腺素E2产生相同的血流增加但不增加微血管通透性，未改变回收的右旋糖酐量。这表明16,16 - 二甲基前列腺素E2后右旋糖酐输出增加主要是由于该药物引起的微血管通透性增加。在其他实验中，H1和H2受体拮抗剂（美吡拉敏和西咪替丁）的组合可防止前列腺素和组胺处理的动物发生胰腺出血。吲哚美辛（一种环氧化酶抑制剂）可防止组胺处理的动物发生出血。我们的结果支持这样的假设，即微血管通透性的变化在该模型中实质出血的发病机制中可能很重要。
