Apte M V, Wilson J S, McCaughan G W, Korsten M A, Haber P S, Norton I D, Pirola R C
Gastrointestinal Unit, Prince of Wales Hospital, Randwick NSW, Australia.
J Lab Clin Med. 1995 May;125(5):634-40.
Ethanol abuse is a well-known association of pancreatitis. The effects of chronic ethanol consumption on pancreatic digestive and lysosomal enzymes may be relevant to the pathogenesis of alcoholic pancreatitis, because pancreatic enzymes play an important role in the development of pancreatic injury. The aims of this study were to determine the effects of ethanol on gene expression and glandular content of pancreatic digestive enzymes and on gene expression of the lysosomal enzyme cathepsin B (known to be capable of activating trypsinogen). Pancreatic content and mRNA levels for lipase, trypsinogen, and chymotrypsinogen were determined in rats that were pair-fed a nutritionally adequate liquid diet with or without ethanol for 4 weeks. mRNA levels for the lysosomal enzyme cathepsin B were also assessed in this model. Ethanol significantly increased the content of lipase in the pancreas. There was a trend toward an increase in trypsinogen and chymotrypsinogen levels; however, these differences were not statistically significant. mRNA levels for lipase, trypsinogen, and chymotrypsinogen were raised in ethanol-fed rats. Ethanol feeding also increased mRNA levels for the lysosomal enzyme cathepsin B. Furthermore, there was a close, statistically significant correlation between changes in mRNA levels and tissue activities of pancreatic digestive and lysosomal enzymes after ethanol consumption. These results suggest that ethanol increases the capacity of the pancreatic acinar cell to synthesize digestive and lysosomal enzymes, thereby increasing the susceptibility of the gland to enzyme-related injury.
乙醇滥用是胰腺炎的一个众所周知的关联因素。长期摄入乙醇对胰腺消化酶和溶酶体酶的影响可能与酒精性胰腺炎的发病机制相关，因为胰腺酶在胰腺损伤的发展中起重要作用。本研究的目的是确定乙醇对胰腺消化酶的基因表达和腺体含量以及对溶酶体酶组织蛋白酶B（已知能够激活胰蛋白酶原）的基因表达的影响。在成对喂养营养充足的液体饮食且添加或不添加乙醇4周的大鼠中，测定脂肪酶、胰蛋白酶原和糜蛋白酶原的胰腺含量和mRNA水平。在该模型中还评估了溶酶体酶组织蛋白酶B的mRNA水平。乙醇显著增加了胰腺中脂肪酶的含量。胰蛋白酶原和糜蛋白酶原水平有升高的趋势；然而，这些差异无统计学意义。在喂食乙醇的大鼠中，脂肪酶、胰蛋白酶原和糜蛋白酶原的mRNA水平升高。喂食乙醇还增加了溶酶体酶组织蛋白酶B的mRNA水平。此外，乙醇摄入后，mRNA水平的变化与胰腺消化酶和溶酶体酶的组织活性之间存在密切的、具有统计学意义的相关性。这些结果表明，乙醇增加了胰腺腺泡细胞合成消化酶和溶酶体酶的能力，从而增加了腺体对酶相关损伤的易感性。
