Wilson J S, Korsten M A, Apte M V, Thomas M C, Haber P S, Pirola R C
Department of Gastroenterology, Prince Henry Hospital, Sydney, Australia.
J Lab Clin Med. 1990 Jun;115(6):749-55.
Both ethanol abuse and protein deficiency result in pancreatic injury. Moreover, these two variables frequently coexist. As lysosomal enzymes may play a role in the initiation of pancreatic injury, the aim of this study was to determine the effects of ethanol consumption and protein deficiency on pancreatic lysosomal stability. For 3 weeks, male Sprague-Dawley rats were match-fed (in groups of four) isocaloric amounts of one of the following liquid diets: (1) protein-sufficient diet, (2) protein-sufficient diet containing ethanol as 36% of the total energy, (3) protein-deficient diet, and (4) protein-deficient diet containing ethanol as 36% of energy. Pancreatic lysosomal stability was assessed by determining (a) latency, as indicated by the percentage increase in lysosomal enzyme activity in pancreatic homogenate induced by Triton X-100, and (b) by the percentage of lysosomal enzyme remaining in the supernatant after sedimentation of the lysosomal pellet from the pancreatic homogenate. Protein deficiency was associated with a decrease in latency and an increase in supernatant enzyme. Ethanol administration was associated with a decreased latency. Both protein-deficient and ethanol-fed animals exhibited higher pancreatic activities of cathepsin B, a lysosomal protease capable of activating trypsinogen. In addition, protein-deficient animals exhibited higher pancreatic activities of acid phosphatase, N-acetyl-glucosaminidase, and beta-glucuronidase. As lysosomal enzymes are postulated to play a role in the initiation of pancreatitis, these results suggest that ethanol consumption and protein deficiency may at least partly exert their toxic effects on the pancreas by altering pancreatic lysosomal stability and increasing the glandular content of cathepsin B.
乙醇滥用和蛋白质缺乏都会导致胰腺损伤。此外，这两个因素经常同时存在。由于溶酶体酶可能在胰腺损伤的起始过程中发挥作用，本研究的目的是确定乙醇摄入和蛋白质缺乏对胰腺溶酶体稳定性的影响。雄性Sprague-Dawley大鼠按组（每组四只）以等热量的方式匹配喂食以下液体饮食之一，持续3周：（1）蛋白质充足饮食；（2）含乙醇占总能量36%的蛋白质充足饮食；（3）蛋白质缺乏饮食；（4）含乙醇占能量36%的蛋白质缺乏饮食。通过以下方式评估胰腺溶酶体稳定性：（a）潜伏期，以Triton X-100诱导的胰腺匀浆中溶酶体酶活性的百分比增加表示；（b）通过从胰腺匀浆中沉淀溶酶体沉淀后上清液中剩余的溶酶体酶百分比来评估。蛋白质缺乏与潜伏期缩短和上清液酶增加有关。给予乙醇与潜伏期缩短有关。蛋白质缺乏和喂食乙醇的动物均表现出组织蛋白酶B（一种能够激活胰蛋白酶原的溶酶体蛋白酶）的胰腺活性较高。此外，蛋白质缺乏的动物表现出酸性磷酸酶、N-乙酰葡糖胺酶和β-葡萄糖醛酸酶的胰腺活性较高。由于推测溶酶体酶在胰腺炎的起始过程中起作用，这些结果表明，乙醇摄入和蛋白质缺乏可能至少部分通过改变胰腺溶酶体稳定性和增加组织蛋白酶B的腺体含量而对胰腺产生毒性作用。
