Zimmermann H, Blaser H, Zimmermann A, Reichen J
Department of Clinical Pharmacology, University of Berne, Switzerland.
J Hepatol. 1994 Feb;20(2):231-9. doi: 10.1016/s0168-8278(05)80063-7.
Secondary biliary cirrhosis in the rat can be induced by bile duct ligation; the aim of the present study was to investigate whether susceptibility to this injury depends on development. Rats aged 4, 7, 14 and 22 weeks were bile-duct ligated or sham operated. Four weeks later, stereologic analysis of the liver was performed and the volume fraction of parenchyma, bile ducts and connective tissue was determined. Microsomal function was assessed in vivo by the aminopyrine breath test and in vitro by determining the microsomal cytochrome P450 content and microsomal lipid composition. In addition, portal pressure was measured. The volume fraction of parenchyma decreased in an age-dependent fashion in bile-duct ligated rats from 64.0 +/- 11.2% in the youngest to 46.4 +/- 8.4% in the oldest age group. This decrease was compensated by an age-dependent increase in both ductular proliferation and fibrosis. Microsomal function both in vivo and in vitro showed an age-dependent deterioration. Microsomal cholesterol and some individual phospholipids showed age-dependent changes. Portal hypertension developed in all bile-duct ligated groups, but portal pressure was significantly lower in the oldest bile-duct ligated groups (16.0 +/- 2.6 cmH2O) compared with other bile-duct ligated groups (around 21 cmH2O). We conclude that susceptibility to the sequelae of chronic cholestasis depends on the stage of development in rats. In experiments using this model, the age of the rats should be explicitly stated.
大鼠继发性胆汁性肝硬化可通过胆管结扎诱导产生；本研究的目的是调查对这种损伤的易感性是否取决于发育阶段。对4周龄、7周龄、14周龄和22周龄的大鼠进行胆管结扎或假手术。四周后，对肝脏进行体视学分析，测定实质、胆管和结缔组织的体积分数。通过氨基比林呼气试验在体内评估微粒体功能，并通过测定微粒体细胞色素P450含量和微粒体脂质组成在体外评估微粒体功能。此外，测量门静脉压力。在胆管结扎的大鼠中，实质的体积分数以年龄依赖性方式降低，从最年轻组的64.0±11.2%降至最年长组的46.4±8.4%。这种降低被小胆管增生和纤维化的年龄依赖性增加所补偿。体内和体外的微粒体功能均显示出年龄依赖性恶化。微粒体胆固醇和一些个别磷脂显示出年龄依赖性变化。所有胆管结扎组均出现门静脉高压，但与其他胆管结扎组（约21 cmH2O）相比，最年长的胆管结扎组门静脉压力显著较低（16.0±2.6 cmH2O）。我们得出结论，大鼠对慢性胆汁淤积后遗症的易感性取决于发育阶段。在使用该模型的实验中，应明确说明大鼠的年龄。
