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

急性肾功能衰竭的机制及治疗研究-内皮素的作用-

基本信息

批准号：
02670273
负责人：
TOMITA Kimio
金额：
$ 1.47万
依托单位：
Tokyo Medical and Dental University
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1990
资助国家：
日本
起止时间：
1990 至 1991
项目状态：
已结题

项目摘要

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.

基础研究1。我研究了内皮素在大鼠急性肾衰竭机制中的作用。双侧肾动脉夹紧45分钟后，肾小球滤过率的降低持续存在。血浆内皮素水平在肾动脉夹后的第二天显示了值。肾脏组织的内皮素含量在第二天的肾小管悬浮液实验中也增加了表明，与胎儿小牛血清孵育后，肾脏髓质小管悬浮液的内皮素产生增加并转化生长因子-beta。这些数据表明，内皮素是通过转化生长因子在肾髓质中合成的 - β可能在组织损伤（例如急性肾衰竭）的情况下。2。研究了内皮素在体液体内稳态调节中的作用，尤其是在体积过载状态下，例如由于急性肾衰竭而导致的肾功能下降。内皮素减少了AVP依赖性cAMP的积累，在被微切除的大鼠收集管道中。在微灌注实验中，内皮素还抑制了大鼠收集导管中AVP依赖性水和氯化物的吸收。因此，内皮素在体积超负荷的状态（例如急性肾衰竭状态）中具有诱导利尿作用。临床研究肾上腺素内皮素水平在急性肾衰竭中升高。肾功能恢复后，它们减少了。一些病例表明，血浆内皮素水平的升高是血清CR水平升高之前的。这也表明内皮素在肾功能恶化中的作用。