Hirano T, Manabe T, Tobe T
First Department of Surgery, Faculty of Medicine, Kyoto University, Japan.
Nihon Geka Gakkai Zasshi. 1992 Dec;93(12):1489-500.
To explore the changes of exorine pancreas in the early stage after ligation of pancreatico-biliary duct (PBD) in rat, we evaluated the changes of serum amylase levels, pancreatic water content as well as the changes of subcellular distribution of cathepsin B in the acinar cells. We also evaluated the lactic dehydrogenase (LDH) discharge from dispersed acini as an index of cellular fragility and cathepsin B leakage from lysosomes as an index lysosomal fragility in vitro study as well as the protective effects of a new synthetic protease inhibitor, nafamostat mesilate (FUT 175) in this model. After ligation of PBD, the serum amylase levels and pancreatic water content, increased significantly compared with those of the control group, but returning to the normal levels at 18 hours. The redistribution of cathepsin B in acinar cells was found and both the cellular and lysosomal fragility increased significantly compared with those of the control groups, shown their peak changes at 12 hours after ligation of PBD. But continuous intravenous administration of FUT 175 (2mg/mg.hr) remarkably attenuated all the parameters. These results indicate the important roles of lysosomal enzyme and lysosomal fragility in the pathogenesis of acute pancreatic injuries in this modes, and the clinical usefulness of FUT 175 in the treatment acute pancreatitis.
为探讨大鼠胰胆管结扎（PBD）术后早期外分泌胰腺的变化，我们评估了血清淀粉酶水平、胰腺含水量的变化以及腺泡细胞中组织蛋白酶B亚细胞分布的变化。我们还评估了体外研究中分散腺泡释放乳酸脱氢酶（LDH）作为细胞脆性指标以及组织蛋白酶B从溶酶体泄漏作为溶酶体脆性指标，以及新型合成蛋白酶抑制剂甲磺酸萘莫司他（FUT 175）在该模型中的保护作用。PBD结扎后，血清淀粉酶水平和胰腺含水量与对照组相比显著升高，但在18小时时恢复至正常水平。发现腺泡细胞中组织蛋白酶B重新分布，与对照组相比，细胞和溶酶体脆性均显著增加，在PBD结扎后12小时显示出峰值变化。但持续静脉注射FUT 175（2mg/mg·hr）可显著减轻所有参数。这些结果表明溶酶体酶和溶酶体脆性在该模型急性胰腺损伤发病机制中的重要作用，以及FUT 175在治疗急性胰腺炎中的临床应用价值。
