Takegoshi K, Nakanuma Y, Ohta M, Thoyama T, Okuda K, Kono N
Department of Internal Medicine, Takaoka City Hospital, Japan.
Liver. 1988 Dec;8(6):330-6. doi: 10.1111/j.1600-0676.1988.tb01012.x.
Intrahepatic cholestasis in paraquat poisoning in man has been thought to be secondary to extensive bile duct injuries, though its exact mechanism remains unsettled. We have examined liver biopsy specimens from two cases of paraquat poisoning. Case 1 (fatal) presented severe intrahepatic jaundice, and liver biopsy showed centrilobular cholestasis with extensive bile duct loss. Ultrastructurally, dilatation of bile canaliculi with decrease of microvilli and thickening of pericanalicular ectoplasm was found in the hepatocytes. Case 2 (alive) showed mild liver dysfunction without jaundice. While liver biopsy showed nonspecific reactive changes with intact bile ducts and ductules, electron microscopy disclosed dilatation of bile canaliculi with decrease of microvilli and thickening of pericanalicular ectoplasm in the hepatocytes, suggesting that damage to the bile secretory apparatus in the hepatocytes develops irrespective of extensive bile duct loss. These findings suggest that bile secretory apparatus in the hepatocytes as well as biliary epithelial cells could be a target of paraquat or its metabolites.
人类百草枯中毒时的肝内胆汁淤积一直被认为是广泛胆管损伤的继发表现,但其确切机制仍未明确。我们检查了两例百草枯中毒患者的肝活检标本。病例1(死亡)出现严重肝内黄疸,肝活检显示小叶中心性胆汁淤积伴广泛胆管缺失。超微结构检查发现,肝细胞内胆小管扩张,微绒毛减少,胆小管周围胞质增厚。病例2(存活)表现为轻度肝功能不全但无黄疸。肝活检显示为非特异性反应性改变,胆管和小胆管完整,而电子显微镜检查发现肝细胞内胆小管扩张,微绒毛减少,胆小管周围胞质增厚,提示肝细胞胆汁分泌装置的损伤与广泛胆管缺失无关。这些发现表明,肝细胞以及胆管上皮细胞中的胆汁分泌装置可能是百草枯或其代谢产物的作用靶点。