论文部分内容阅读
目的:研究它克雷默(FK506)诱发肾低灌注的机制并筛选相应拮抗药物。方法:利用离体肾灌流模型,实验分为6组。灌流过程中每15min,对肾功能指标进行测定,同时测定了灌流液和尿中内皮素的浓度。其中4组用生理盐水及不同浓度的FK506进行灌流,建立对照和低灌流模型,另外2组用于测定内皮素受体拮抗剂FR139317和钙通道组滞剂地尔硫卓对肾低灌流的作用。结果:灌流液中加入10μmol/L的FK506诱发肾脏低灌流,肾灌流量、肾小球滤过率明显下降,肾灌流阻力明显升高,灌流液和尿液中内皮素水平升高。用FR139317和地尔硫卓分别与FK506一起灌流,地尔硫卓完全纠正FK506所引起的肾小球滤过率下降和灌流阻力的升高,FR139317部分纠正了肾小球滤过率改变,但对灌流阻力变化的影响不明显。结论:在FK506诱发的急性肾低灌注中,内皮素可能起重要作用,地尔硫卓能够完全拮抗FK506引起的肾脏低灌流。
OBJECTIVE: To study the mechanism of KK (FK506) induced hypoperfusion and to screen for the corresponding antagonist. Methods: In vitro renal perfusion model, the experiment is divided into 6 groups. Every 15 minutes during perfusion, the renal function was measured, and the concentrations of endothelin in perfusate and urine were also determined. Four groups were perfused with normal saline and different concentrations of FK506 to establish a control and hypoperfusion model. The other two groups were used to determine the effects of endothelin receptor antagonist FR139317 and diltiazem, a calcium channel blocker, on renal hypoperfusion. Results: FK506 with 10μmol / L was added into the perfusate solution to induce renal hypoperfusion. The renal perfusion and glomerular filtration rate were significantly decreased. The renal perfusion resistance was significantly increased. The endothelin level in perfusate and urine increased. Perfusion of FK506 with FR139317 and diltiazem, diltiazem completely corrected the decrease of glomerular filtration rate and perfusion resistance caused by FK506. FR139317 partially corrected the change of glomerular filtration rate but had no effect on the change of perfusion resistance Not obvious. CONCLUSION: Endothelin may play an important role in FK506-induced acute renal hypoperfusion. Diltiazem can completely antagonize FK506-induced renal hypoperfusion.