The study on molecular biological mechanisms and therapy of sodiam and acid disturbance in renal failure

慢性肾功能衰竭患者尿钠和酸排泄减少。肾脏中的几种离子转运蛋白参与钠和酸的排泄。我们重点研究了分泌型Na-K-2Cl协同转运蛋白（NKCC 1）。为了了解NKCC 1在体液平衡调节中的作用，我们研究了NKCC 1在小鼠和大鼠肾单位中的分布。NKCC 1 mRNA在小鼠的内髓集合管（IMCD）和大鼠的外髓集合管（OMCD）中表达最丰富。慢性代谢性酸中毒引起的管理NH 4C 1和两天的脱水引起的NKCC 1 mRNA表达的显着增加，在收集管和NKCC 1蛋白表达的OMCD。接下来，为了研究脱水上调NKCC 1 mRNA表达的机制，研究了高渗和加压素（AVP）对其表达的影响。高渗和AVP可增加NKCC 1 mRNA的表达。这些结果表明，AVP，直接或间接通过增加髓质渗透压，调节NKCC 1的表达。由于V2加压素受体在慢性肾功能衰竭中下调，AVP在肾功能衰竭患者的钠和酸排泄中起重要作用。

Patients with chronic renal failure showed decreased urinary excretion of sodium and acid. Several ion transporters in the kidney participate in sodium and acid excretion. We focused on secretory type Na-K-2Cl cotransporter (NKCC1). To know the role of NKCC1 in the regulation of body fluid homeostasis, we investigated the distribution of NKCC1 along the nephron in mouse and rat. NKCC1 mRNA expression was most abundant in inner medullary collecting ducts (IMCD) in mouse and outer medullary collecting ducts (OMCD) in rat. Chronic metabolic acidosis induced by the administration of NH4C1 and two-days dehydration caused a significant increases of NKCC1 mRNA expression in collecting ducts and NKCC1 protein expression in OMCD. Next, to examine the mechanisms of the up-regulation of NKCC1 mRNA expression by dehydration, the effects of hyperosmolality and vasopressin (AVP) on its expression were studied. Hyperosmolality and AVP increased NKCC1 mRNA expression in OMCD. These results show that AVP, directly or indirectly through the increase in medullary osmolality, regulates NKCC1 expression. Since V2 vasopressin receptors were downregulated in chronic renal failure, AVP plays an important role in sodium and acid excretion in patients with renal failure.