Vakil N, Sharma A, Yagil Y
Department of Medicine, University of Rochester, New York 14642.
Hepatology. 1994 Feb;19(2):457-63.
In an earlier study we showed that bile duct-ligated rats were highly susceptible to gentamicin nephrotoxicity and that oral calcium administration had a pronounced protective effect. The mechanism by which this occurs is unclear. Because cations compete with gentamicin for tubule binding sites, it has been suggested that the increased susceptibility of the kidney to gentamicin after bile duct ligation might result from decreased cation excretion. The aim of this study was to determine the effect of bile duct ligation on calcium excretion in relation to overall renal function. Male Sprague-Dawley rats underwent bile duct ligation and division. Pair-fed sham-operated rats served as controls. Metabolic and clearance studies were carried out at 3, 5, 7, 14 and 21 days after surgery. Urine output was higher in bile duct-ligated rats, and they excreted more calcium at 3, 5, 7 and 14 days, while excreting less sodium than controls. We conclude that after bile duct ligation, there is increased calcium excretion, which is independent of the abnormality in sodium excretion. Enhanced nephrotoxicity with aminoglycosides in the bile duct-ligated rat model cannot be explained by decreased calcium excretion.
在一项早期研究中,我们发现胆管结扎大鼠对庆大霉素肾毒性高度敏感,口服钙具有显著的保护作用。其发生机制尚不清楚。由于阳离子与庆大霉素竞争肾小管结合位点,有人认为胆管结扎后肾脏对庆大霉素敏感性增加可能是由于阳离子排泄减少所致。本研究的目的是确定胆管结扎对钙排泄的影响及其与整体肾功能的关系。雄性Sprague-Dawley大鼠接受胆管结扎和切断手术。成对喂养的假手术大鼠作为对照。在术后3、5、7、14和21天进行代谢和清除率研究。胆管结扎大鼠的尿量较高,在术后3、5、7和14天排出的钙更多,而排出的钠比对照组少。我们得出结论,胆管结扎后钙排泄增加,这与钠排泄异常无关。胆管结扎大鼠模型中氨基糖苷类药物增强的肾毒性不能用钙排泄减少来解释。