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

肾衰竭钠酸紊乱的分子生物学机制及治疗研究

• 批准号: 10671000
• 负责人: NONOGUCHI Hiroshi
• 金额: $ 2.24万
• 依托单位: Kumamoto University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1998
• 资助国家: 日本
• 起止时间: 1998 至 1999
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-10671000/
• 关键词: Chronic renal failure; Vesopressin; V2 receptor; Via receptor; NKCC1; Collecting cluct; Osmolality; 抗利尿ホルモン(ADH); Vla受容体; NKCC1; 髄質外層集合尿細管; オキシトシン; 腎不全; Na-K-2Cl cotransporter; 集合尿細管; 脱水; 代謝性アシドーシス

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.

慢性肾衰竭的患者显示钠和酸的尿排泄减少。肾脏中的几个离子转运蛋白参与钠和酸排泄。我们专注于分泌类型Na-K-2Cl共转运蛋白（NKCC1）。为了了解NKCC1在体液体内稳态调节中的作用，我们研究了NKCC1在小鼠和大鼠中沿肾单位的分布。 NKCC1 mRNA表达在大鼠的小鼠和外髓外收集管（OMCD）中的内髓质收集管（IMCD）中最丰富。 NH4C1的给药诱导的慢性代谢性酸中毒和两天脱水导致NKCC1 mRNA表达在收集OMCD中的导管和NKCC1蛋白表达时显着增加。接下来，为了检查NKCC1 mRNA表达的上调的机制，研究了高透明和加压素（AVP）对其表达的影响。高胶质和AVP增加了OMCD中NKCC1 mRNA的表达。这些结果表明，通过髓质渗透压的增加，AVP直接或间接地调节NKCC1表达。由于V2加压素受体在慢性肾衰竭中被下调，因此AVP在肾衰竭患者的钠和酸排泄中起重要作用。

项目成果

K. Itoh: "Gene regulation of atrial natriuretic peptide A, B, and C receptors in rat glomerule"Exp. Nephrol.. 7. 328-336 (1999)

K. Itoh：“大鼠肾小球中心房钠尿肽 A、B 和 C 受体的基因调控”实验。

H. Nonoguchi: "Regulation of the renal Na/K/2cl cotransporter gene physiological modulation in health and abnormal function in disease"Exp. Nephrol. 6. 272-276 (1998)

H. Nonoguchi：“健康中肾 Na/K/2cl 协同转运蛋白基因生理调节和疾病中功能异常的调节”Exp。

K.Itoh: "Gene regulation of atrial natriuretic peptide A,B,and C receptors in rat glomeruli" Exp. Nephrol.7(in press). (1999)

K.Itoh：“大鼠肾小球中心房钠尿肽 A、B 和 C 受体的基因调控”实验。

Y. Nakayama: "Intranephron distributiion and regulation of endothelin-converting enzyme-1 in cyclosporin A-induced acute renal failure in rats"J. Am. Soc. Nephrol.. 10. 562-571 (1999)

Y. Nakayama：“环孢素 A 诱导的大鼠急性肾功能衰竭中内皮素转换酶 1 的肾内分布和调节”J。

H.Nonoguchi: "Renal effects of temocapril hydrochloride (CS-622) in patienls with benign nephrosclerosis" Nephrology. 4. 183-186 (1998)

H.Nonoguchi：“盐酸替莫普利 (CS-622) 对良性肾硬化患者的肾脏影响”肾脏病学。