Grady T, Saluja A, Kaiser A, Steer M
Department of Surgery, Beth Israel Hospital, Boston, Massachusetts 02215, USA.
Am J Physiol. 1996 Jul;271(1 Pt 1):G20-6. doi: 10.1152/ajpgi.1996.271.1.G20.
Acute pancreatitis is characterized by hyperamylasemia, pancreatic edema, and the presence of activated digestive enzymes within the pancreas. The secretagogue-induced model of acute pancreatitis is also characterized by pancreatic acinar cell vacuolation, subcellular redistribution of lysosomal hydrolases, and a fall in pancreatic glutathione levels. We have performed time-dependence studies to determine the sequence with which these phenomena appear and to establish their cause-and-effect relationship. Evidence of lysosomal enzyme redistribution and trypsinogen activation within the pancreas could be detected within 10-15 min of the onset of supramaximal secretagogue stimulation, while hyperamylasemia (30 min), pancreatic edema (60 min), and acinar cell vacuolation (60 min) occurred at later times. Pancreatic glutathione levels were either unchanged (15 and 30 min) or elevated (60 min) during the early times of supramaximal stimulation and were only noted to be decreased at a later time. These results support the conclusion that intrapancreatic digestive enzyme activation, possibly occurring by a mechanism involving lysosomal hydrolase redistribution, is an early and likely a critical event in the evolution of secretagogue-induced pancreatitis but that glutathione depletion is neither early nor critical to the evolution of this model of pancreatitis.
急性胰腺炎的特征为高淀粉酶血症、胰腺水肿以及胰腺内存在活化的消化酶。促分泌剂诱导的急性胰腺炎模型还具有胰腺腺泡细胞空泡化、溶酶体水解酶的亚细胞重新分布以及胰腺谷胱甘肽水平下降的特征。我们进行了时间依赖性研究，以确定这些现象出现的顺序并建立它们的因果关系。在超最大促分泌剂刺激开始后的10 - 15分钟内，可检测到胰腺内溶酶体酶重新分布和胰蛋白酶原激活的证据，而高淀粉酶血症（30分钟）、胰腺水肿（60分钟）和腺泡细胞空泡化（60分钟）则在较晚时间出现。在超最大刺激的早期，胰腺谷胱甘肽水平要么未改变（15分钟和30分钟），要么升高（60分钟），只是在较晚时间才被注意到降低。这些结果支持以下结论：胰腺内消化酶激活可能通过涉及溶酶体水解酶重新分布的机制发生，是促分泌剂诱导的胰腺炎发展过程中的一个早期且可能关键的事件，但谷胱甘肽耗竭对该胰腺炎模型的发展既不是早期事件也不是关键事件。
