<Original Articles>Effect of Ethanol on Pancreatic Lysosomes in Rats : A Possible Mechanism for Alcoholic Pancreatitis

Abstract

Four-hour infusion of ethanol (0. 5 g/kg・hr) and additional 2-hour infusion of caerulein (0. 2 μg/kg・hr) and secretin (0. 2 CU/kg・hr) caused hyperamylasemia, pancreatic edema and pancreatic histological changes such as interstitial edema and acinar cell vacuolization in the rat. Such a combined treatment also induced a redistribution of lysosomal enzyme cathepsin B, from the lysosomal fraction to the zymogen fraction in subcellular fractionation. Only ethanol infusion caused marginal changes in all these parameters. Moreover, 4-hour pre-infusion of ethanol caused a significant increase in pancreatic cathepsin B output stimulated by caerulein (0. 2 μg/kg・hr) and secretin (0. 2 CU/kg・hr) compared with the control rats. This pretreatment of ethanol also caused a significant increase in cathepsin B/amylase output ratio. These results indicate that ethanol administration, if combined with exocrine stimulation, causes a colocalization of lysosomal hydrolases with digestive enzymes in the same subcellular compartment as well as in the pancreatic ductal space, and also suggest one possible mechanism for alcoholic pancreatitis both within and outside the acinar cells, since cathepsin B can activate trypsinogen.

4時聞のエタノール静脈内投与(0. 5g/kg・hr)とさらに2時間のセルレイン(0. 2μg/kg・hr)とセクレチン(0. 2 CU/kg・hr)投与により, ラットにおいて, 高 amylase 血症, 膵浮腫, 組織学的に膵腺房細胞の空胞化が出現した. これらの処置により, ライソゾーム酵素である cathepsin B のライソゾーム分画よりチモーゲン分画への再分布も観察されるとともにセルレインとセクレチン刺激下での膵液中への cathepsin B 分泌量も増加した. エタノール単独群では軽度な変化のみ観察された. これらの結果は, エタノール投与と膵外分泌刺激により, 膵腺房細胞中および膵管腔でのライソゾーム酵素と膵消化酵素の共存を意味するものであり, cathepsin B は trypsinogen を活性化し得ることより, アルコール性膵炎の解明にひとつの可能性を示唆するものと考えられた.