肾病综合征大鼠肾小球血管紧张素Ⅱ受体功能变化及其机制

Changes of angiotensin Ⅱ receptors on glomeruli in rats with nephrotic syndrome

目的 :探讨肾素 血管紧张素系统 (RAS)在肾病综合征发病机制中的作用 方法 :放射配基结合实验测定血管紧张素Ⅱ (AngⅡ )与阿霉素肾病大鼠 (ADR)肾小球的结合 ,以及血管紧张素转换酶抑制剂 (ACEI)对结合的影响 ;同时应用放免分析法测定相应的血浆AngⅡ和醛固酮水平。 结果 :①大鼠肾小球具有特异性、可逆性、可饱和性、竞争性和高亲和力的AngⅡ结合位点。②肾病组血浆AngⅡ和醛固酮水平、受体的解离常数 (Kd)与对照组比较差异无显著性意义 (P >0 0 5 ) ,但肾病组肾小球AngⅡ受体的最大结合容量 (Bmax)较对照组显著下降 (P <0 0 1)。应用依那普利治疗后 ,两组大鼠肾小球AngⅡ受体的Bmax均上升 ,组间无显著性差异 (P >0 0 5 )。 结论 :①肾小球AngⅡ结合位点是AngⅡ的受体。②ADR肾内RAS处于活化状态 。

Objective:To investigate the pathophysilogic role of renal reinin angiotensin system in rats with nephrotic syndrome. Methodology:Sixty four male SD rats with the weight of 220 to 360g, were randomly divided into four groups. They were Group A ( n =20)-normal control rats, group B ( n =20)-nephrotic syndrome (NS) rats treated with adriamycin (ADR), group C ( n =12) NS rats with ADR plus enalapril, and group D ( n =12)-normal rats treated with enalapril. Binding of isolated glomerular angiotensin Ⅱ (Ang Ⅱ) receptors with its ligand was examined by radioligand binding technique following. The levels of plasma Ang Ⅱ and aldosterone were detected by RIA. Furthermore, the effects of angiotensin converting enzyme inhibitor (ACEI) on those binding were also determined by RIA. Results:The isolated glomeruli expressed plenty of binding sites for 125 I AngⅡ, which are specific, reversible, saturable and high in affinity. The receptor density (B max) in NS rats was significantly lower than that in normal control (NS vs normal control, (1971±573) vs (2563±854) fmol/mg, t =-80 3, t 0 01 =3 26, P <0 01), while there were not significant differences in the affinity (Kd), and levels of plasma Ang Ⅱ and aldosterone concentrations between those two groups. The lower B max in NS rats was significantly ameliorated as near as that in normal control rats after administration of ACEI [NS vs normal control (2656±493),(2764±528) fmol/mg, t =0 368, t 0 01 =2 57, P >0 05]. Conclusion:Our data suggested that the binding sites on glomeruli for Ang Ⅱ were the receptors of Ang Ⅱ. The rennin angiotensin system of kidney in nephrotic syndrome induced by ADR was activated, which resulted in the decrease of receptor density (B max) or down regulation.