Hirano T, Manabe T, Calne R, Printz H
First Department of Surgery, Faculty of Medicine, Kyoto University, Japan.
Nihon Geka Hokan. 1992 Jul 1;61(4):320-33.
This study was designed to evaluate the effects of direct pancreatic surface cooling on the exocrine pancreas. We measured the changes in serum amylase levels, pancreatic water, amylase and cathepsin B as a lysosomal enzyme, content, histological changes of acinar cells, and the subcellular distribution of cathepsin B after 1-2- and 3-hours of direct pancreatic cooling in rats. In addition, we evaluated the in-vivo amylase and cathepsin B output stimulated by caerulein, in-vitro lysosomal and mitochondrial fragility as well as the pancreatic adenylate energy metabolism. 2-hours cooling showed slight yet significant changes, but 3-hours cooling caused most significant changes including hyperamylasemia, increased pancreatic amylase content and very mild histological changes. Furthermore, 3-hours cooling caused a remarkable redistribution of cathepsin B activity from the lysosomal fraction to the heavier zymogen fraction, and colocalization of the lysosomal enzyme with the digestive enzyme, the impaired amylase and cathepsin B output into pancreatic juice stimulated by caerulein as well as the accelerated fragility of lysosomes and mitochondria, and impaired pancreatic adenylate energy metabolism. These results indicate the impaired exocrine pancreatic functions induced by direct pancreatic cooling injury induced by cooling as shown in the other models of experimental pancreatitis. Moreover, this cooling model of pancreatitis seems to be useful in understanding the early events in the pathogenesis of acute pancreatitis, and we must take these "cold" injuries of exocrine pancreas into considerations, particularly in the pancreas transplantation and in other major abdominal surgeries where the pancreas is exposed to cooling.
本研究旨在评估直接胰腺表面降温对外分泌胰腺的影响。我们测量了大鼠胰腺直接冷却1小时、2小时和3小时后血清淀粉酶水平、胰腺水分、淀粉酶和作为溶酶体酶的组织蛋白酶B含量、腺泡细胞的组织学变化以及组织蛋白酶B的亚细胞分布。此外,我们评估了由蛙皮素刺激的体内淀粉酶和组织蛋白酶B的分泌、体外溶酶体和线粒体的脆弱性以及胰腺腺苷酸能量代谢。2小时的冷却显示出轻微但显著的变化,但3小时的冷却导致了最显著的变化,包括高淀粉酶血症、胰腺淀粉酶含量增加和非常轻微的组织学变化。此外,3小时的冷却导致组织蛋白酶B活性从溶酶体部分显著重新分布到较重的酶原部分,溶酶体酶与消化酶共定位,蛙皮素刺激的淀粉酶和组织蛋白酶B分泌到胰液中受损,以及溶酶体和线粒体的脆弱性加速,胰腺腺苷酸能量代谢受损。这些结果表明,如其他实验性胰腺炎模型所示,直接胰腺冷却损伤会导致外分泌胰腺功能受损。此外,这种胰腺炎冷却模型似乎有助于理解急性胰腺炎发病机制中的早期事件,并且我们必须考虑外分泌胰腺的这些“冷”损伤,特别是在胰腺移植以及胰腺暴露于冷却的其他大型腹部手术中。