Research of the mechanism and treatment for acute renal failure-role of endothelin-

基础研究1.我研究了内皮素在大鼠急性肾功能衰竭发病机制中的作用。夹闭双侧肾动脉45min后，肾小球滤过率持续下降。血浆内皮素水平在肾动脉阻断后第2天开始升高。肾小管悬液实验显示，与胎牛血清和转化生长因子-β孵育后，肾髓质小管悬液中内皮素的生成增加。这些数据表明，在急性肾功能衰竭等组织损伤的情况下，内皮素可能是通过转化生长因子-β在肾髓质中合成的。研究了内皮素在体液平衡调节中的作用，特别是在容量超负荷状态下，如急性肾功能衰竭所致的肾功能下降。内皮素减少显微解剖大鼠集合管中AVP依赖的cAMP积聚。在微灌流实验中，内皮素还抑制大鼠集合管对AVP依赖的水和氯化物的重吸收。因此，在容量超负荷状态下，如急性肾功能衰竭，内皮素具有诱导利尿的作用。临床研究急性肾功能衰竭患者血浆内皮素水平升高。随着肾功能的恢复而降低。部分病例显示血浆内皮素水平升高先于血清肌酐水平升高。这也提示内皮素在肾功能恶化中的作用。

BASIC STUDY1. I investigated the role of endothelin in the mechanisms of acute renal failure in rat. Decreases in glomerular filtration rate persisted after 45 minutes clamp of bilateral renal artery. Plasma endothelin levels showed the value at the 2nd day after clamp of renal artery. Endothelin content of renal tissue also increased at 2nd day Renal tubule suspension experiments showed that endothelin production increased in renal medullary tubule suspension after incubation with fetal calf serum and transforming growth factor -BETA. These data suggest that endothelin was synthesized in renal medulla by transforming growth factor - BETA possibly in cases of tissue damage such as acute renal failure.2. Role of endothelin in the regulation of body fluid homeostasis was investigated especially in the state of volume overload such as decrease in renal function due to acute renal failure. Endothelin decreased AVP-dependent cAMP accumulation in microdissected rat collecting duct. In microperfusion experiments, endothelin also inhibited AVP-dependent water and chloride reabsorption in rat collecting duct. Therefore endothelin has roles to induce diuresis in the state of volume overload such as acute renal failure.CLINICAL STUDYPlasma endothelin levels were increased in acute renal failure. They decreased following the recovery of renal function. Some case showed that raises in plasma endothelin level preceded the increase in serum Cr levels. This also suggest the role of endothelin in deterioration of renal function.