内皮素受体拮抗剂防治缺血性急性肾衰的实验研究

Endothelin receptor antagonists in the management of ischemic acute renal failure

为探讨内皮素（ＥＴ）受体拮抗剂对缺血性急性肾衰（ＩＡＲＦ）的防治作用，对大鼠ＩＡＲＦ模型，再灌注６０分钟自股动脉分别灌入生理盐水，选择性内皮素Ａ受体（ＥＴＡ）拮抗剂ＰＤ１４７９５３和非选择性内皮素受体（ＥＴＲ）拮抗剂ＰＤ１４５０６５，观察肾皮质血流、肾功能和肾组织学改变。结果：与对照组比较，ＥＴＲ拮抗剂可明显增加肾缺血再灌注后的肾皮质血流（Ｐ＜０．０１），减轻肾功能损害（Ｐ＜０．０１）及组织学改变，其中以非选择性ＥＴＲ拮抗剂效果更好。结果认为：ＥＴ升高及其两种受体亚型的上调是ＩＡＲＦ发生发展的重要因素，外源性提供ＥＴＲ拮抗剂阻断ＥＴ生物学作用是防治ＩＡＲＦ的又一新途径。

PD 147953 , a selective endothelin A receptor antagonist (ETA) and PD 145065 , a non selective endothelin receptor antagonist were infused continuously into the abdominal aorta for 3 hours on rat models of ischemic acute renal failure (IARF). Changes in renal cortex blood flow, renal function and the renal morphological structure were observed. The results revealed that the non selective endothelin receptor antagonist could markedly improve the renal cortex bood flow ( P <0.01) and provide significant protection to the renal function ( P <0.01) and the morphological structure of rat kidney following renal ischemia reperfusion injury. Non selective endothelin receptor antagonist has been more effective than the selective. It was concluded that an increase of ET and an upregulation of endothelin receptor played an important role in the pathogenesis of ischemic acute renal failure. Intravenous infusion of exogenous non selective endothelin receptor antagonist might be a new means for the prevention and treatment of IARF.