Molecular biological analysis of the mechanism of acute renal failure

本实验研究了缺血及环孢素A诱导的急性肾功能衰竭大鼠肾组织内皮素-1蛋白及mRNA、内皮素转换酶蛋白及mRNA、A型内皮素受体mRNA、B型内皮素受体mRNA的表达及调控。缺血损伤或环孢素A注射后30min至数小时内，ET-1mRNA开始升高。A型内皮素受体mRNA在两型急性肾功能衰竭中均降低。缺血性急性肾功能衰竭时B型内皮素受体基因表达增加。但在环孢素所致的急性肾功能衰竭时，则呈下降趋势。环孢素诱导的急性肾功能衰竭时内皮素转换酶蛋白和mRNA的表达降低。为了阐明抑制内皮素转换酶蛋白和基因表达的机制，我们研究了培养内皮细胞对内皮素酶的调节作用。内皮素-1通过B型内皮素受体对内皮素转换酶蛋白和mRNA产生抑制作用。提示急性缺血性肾功能衰竭时肾功能损害可能通过A型内皮素受体的减少和B型内皮素受体的增加而得到保护。环孢素所致的急性肾功能衰竭，其肾功能损害可能通过A型内皮素受体的减少和B型内皮素受体转换酶的降低而发挥保护作用。

We investigated the expression and regulation of endothelin-1 protein and mRNA,endothelin converting enzyme protein and mRNA,A type endothelin receptor mRNA,B type endothelin receptor mRNA in ischemic and cyclosporine-induced acute renal failure. Endothelin-1 mRNA started to increase from 30 minutes to several hours after ischemic insult or cyclosporine administration. A type endothelin receptor mRNA decreased in both types of acute renal failure. B type endothelin receptor mRNA increased in ischemic acute renal failure. However, it decreased in cyclosporine-induced acute renal failure. Endothelin converting enzyme protein and mRNA decreased in cyclosporine-induced acute renal failure. To elucidate the mechanism of inhibition of endothelin converting enzyme protein and mRNA,regulation of endothelin converting enzyme was investigated in cultured endothelial cells. Endothelin-1 has an inhibitory effect on endothelin converting enzyme protein and mRNA through B type endothelin receptor. These data suggests that impairments of renal function may be protected by the decrease in A type endothelin receptor and increase in B type endothelin receptor in ischemic acute renal failure. As for cyclosporine-induced acute renal failure, impairments of renal function may be protected by the decrease in A type endothelin receptor and decrease in endothelin converting enzyme through B type endothelin receptor.