Perez G, Rietberg B, Owens B, Parker T, Obaya H, Schiff E
Nutr Metab. 1980;24(6):409-16. doi: 10.1159/000176358.
Urea synthesis was examined in experimental uremia using the isolated perfused rat liver in order to assure strict control of substrate (NH4Cl) presented to the liver. Acute uremia was created in female Sprague-Dawley rats by bilateral nephrectomy (n = 7) 48 h prior to studies. Chronic uremia (8--14 weeks) was produced by right nephrectomy and segmental infarction of the left kidney in 7 rats. At infusion rates of NH4Cl (8.3 mumol/min) which resulted in prehepatic perfusate ammonia levels approximately twice the previously described Km value, livers of chronically uremic rats had slightly higher rates of urea production than controls (controls: 0.41 +/- 0.03; chronic uremia: 0.54 +/- 0.04 mumol/min/g of wet liver weight; p less than 0.02). In acute uremia, urea production was higher (0.66 +/- 0.05 mumol/min/g) than in sham-operated rats (0.59 +/- 0.05 mumol/min/g) but the differences did not achieve statistical significance. Simultaneously performed taurocholate transport studies did not reveal significant functional differences between the livers of uremic and control animals. The data suggest that urea production by livers of uremic rats is increased when compared to that of control animals.
为确保严格控制进入肝脏的底物(氯化铵),采用离体灌注大鼠肝脏研究实验性尿毒症中的尿素合成。在研究前48小时,通过双侧肾切除术(n = 7)对雌性Sprague-Dawley大鼠造成急性尿毒症。通过右肾切除术和左肾节段性梗死对7只大鼠造成慢性尿毒症(8 - 14周)。在氯化铵输注速率为8.3 μmol/分钟时,导致肝前灌注液氨水平约为先前描述的Km值的两倍,慢性尿毒症大鼠肝脏的尿素生成速率略高于对照组(对照组:0.41±0.03;慢性尿毒症组:0.54±0.04 μmol/分钟/克湿肝重;p < 0.02)。在急性尿毒症中,尿素生成高于假手术大鼠(0.66±0.05 μmol/分钟/克对0.59±0.05 μmol/分钟/克),但差异无统计学意义。同时进行的牛磺胆酸盐转运研究未显示尿毒症和对照动物肝脏之间存在显著功能差异。数据表明,与对照动物相比,尿毒症大鼠肝脏的尿素生成增加。