内皮素受体拮抗剂PD142893对梗阻性黄疸大鼠并发肾功能损害的影响

目的：了解梗阻性黄疸（obstructive jaundice，OJ）大鼠模型血浆和肾组织内皮素（endothelin，ET）含量变化对肾功能的影响以及应用ET受体拮抗剂PD142893后的变化。方法：假手术组、OJ组及OJ＋药物组共32只Wistar大鼠分别于术后5、10、15和20d（每组n=8）采用放射免疫法测定血浆和肾匀浆的ET含量，同时测定血清TBIL、肌酐清除率，对肾脏行光镜下病理组织形态学观察。结果：在OJ组和OJ＋药物组中血清TBIL含量、血浆和肾组织匀浆中ET含量随梗阻时间延长而明显增加；OJ组在术后5d即表现为肌酐清除率下降，随梗阻时间延长而加重并伴有肾脏病理形态的进行性改变，而OJ＋药物组对比OJ组相应的改变出现的较晚；在非药物治疗组中，肌酐清除率与血浆和肾组织匀浆中ET含量呈负相关。结论：OJ时的高胆红素血症是导致肾功能损害的原因之一，胆色素对肾脏有直接的毒性作用；OJ引起血浆和肾组织中ET的病理性升高，由其介导的多种生物学效应是最终导致肾功能损害的重要原因；肽类非选择性ET受体拮抗剂PD142893对OJ大鼠的肾脏具有保护作用。

Effect of endothelin receptor antagonist PD142893 on renal function impairment of rats with obstructive jaundice

Objective： To study the effect of endothelin （ET） receptor antagonist PD142893 on renal function impairment of rats with obstructive jaundice. Methods： Ninety-six Wistar rats were randomized into three groups （n=32）, ham operation group （S）, bile duct ligation group （OJ） and bile ligation plus PD142893 group （OJ＋D）. The levels of plasma and kidney ET, serum total bilirubin （TBIL）, creatinine clearance rate （Ccr） were measured by specific radioimmunological method. Renal histological changes were observed with optical microscopy. Result： The increase of ET in plasma and renal tissue, serum TBIL in OJ and OJ＋D groups were time-dependent. After 5 days, the decrease of Ccr and the degree of renal tissue impairment in OJ group were also on time dependent. The changes occurred in OJ＋D group were later than that in OJ group, Conelusions： Hyperbilirubinemia may be one of the reasons which induce renal function impairment （RFI） and porphobilin can impair renal tissue directly.