Volentine G D, Ogden K A, Kortje D K, Tuma D J, Sorrell M F
Hepatology. 1987 May-Jun;7(3):490-5. doi: 10.1002/hep.1840070313.
Ethanol administration inhibits hepatic protein and glycoprotein secretion. Previous studies have shown that the metabolism of ethanol is required for this effect. Experiments were designed to determine whether acetaldehyde, the first metabolite of ethanol oxidation, mediated the ethanol-induced secretory defect in rats with normal and stimulated (inflammation-induced) rates of hepatic protein secretion. This study used cyanamide, an aldehyde dehydrogenase inhibitor, to correlate enhanced acetaldehyde levels with an increased ethanol-induced inhibition of hepatic protein secretion. Inflammation was induced by turpentine 24 hr prior to cyanamide (5 mg per kg body weight) or saline pretreatment. Nonfasted rats were intragastrically gavaged with ethanol (4 to 6 gm per kg body weight) or isocaloric glucose 1 hr following pretreatment. [3H]Fucose and/or [14C]leucine were injected intravenously 2 hr following intubation. With elevated levels of acetaldehyde, the ethanol-induced impairment of secretion of labeled proteins and their parallel retention in the liver were markedly potentiated. During inflammation, this inhibition of secretion by ethanol was maintained and further increased with cyanamide pretreatment. These results indicate that the ethanol-induced impairment of hepatic glycoprotein secretion is mediated by acetaldehyde in both normal and inflammation-stimulated animals.
给予乙醇会抑制肝脏蛋白质和糖蛋白的分泌。先前的研究表明，乙醇的代谢对于这种作用是必需的。设计实验以确定乙醛（乙醇氧化的第一种代谢产物）是否介导了正常和刺激（炎症诱导）肝脏蛋白质分泌速率的大鼠中乙醇诱导的分泌缺陷。本研究使用醛脱氢酶抑制剂氨甲环酸，将升高的乙醛水平与乙醇诱导的肝脏蛋白质分泌抑制增加相关联。在氨甲环酸（每千克体重5毫克）或生理盐水预处理前24小时，用松节油诱导炎症。预处理后1小时，对非禁食大鼠经胃内灌胃给予乙醇（每千克体重4至6克）或等热量葡萄糖。插管后2小时静脉注射[3H]岩藻糖和/或[14C]亮氨酸。随着乙醛水平升高，乙醇诱导的标记蛋白质分泌受损及其在肝脏中的平行滞留明显增强。在炎症期间，乙醇对分泌的这种抑制作用得以维持，并且经氨甲环酸预处理后进一步增强。这些结果表明，在正常和炎症刺激的动物中，乙醇诱导的肝脏糖蛋白分泌受损均由乙醛介导。
