内皮素受体拮抗剂联合内皮源血管松弛因子防治大鼠缺血性急性肾衰竭

目的:观察内皮素受体拮抗剂PD145065联合内皮源血管松驰因子NO生理性前体L-arginine对大鼠缺血性急性肾衰竭是否有防治作用.方法:采用阻断大鼠双侧肾脏血流45 min再灌注24 h之急性肾缺血再灌注动物模型,观察内皮素受体拮抗剂PD145065或内皮源血管松驰因子NO生理性前体L-arginine或两者联合应用,对再灌注24 h后大鼠肾组织病理变化和肾功能的影响.结果:PD145065或L-arginine单独作用均可明显减轻肾缺血再灌注后的肾组织病理损害,提高肾小球滤过率,改善肾功能.其中,两者联合应用的效果比单独使用的效果更好.结论:缺血性急性肾衰竭时,内皮素升高及其受体上调是缺血性急性肾衰竭发生发展的重要因素,外源性给予内皮素受体拮抗剂可阻断内皮素的生物作用,并且联合内皮源血管松弛因子的应用效果更佳.这是防治缺血性急性肾衰竭的又一新途径.

A Study on Combined Treatment with Endothelin Receptor Antagonist and Endothelium Derived Relaxing Factor in Rat Ischemic Acute Renal Failure

Objective:To investigate PD 145065, an endothelin receptor antagonist (ETRA) and L-Arginine,a donor of endothelium derived relaxing factor(EDRF) in preventing ischemic acute renal failure (IARF).Methods:Acute renal ischemic/reperfusion animal model of bilateral nephrectomy in rats were employed. PD 145065 and L-arginine alone or in combination were injected for 24 hours. Renal histology and renal function were examined.Results:Renal histology and function were significantly improved by PD 145065 and L-arginine alone or in combination. PD 145065 combined with L-arginine was better than PD 145065 or L-arginine alone.Conclusion:Exogenic endothelium receptor antagonist can block the biological effect of endothelium, and shows better effect when combining with endothelium derived relaxing factor. We believe that endothelium receptor antagonist may be a new way to prevent and treat ischemic renal failure.