Mechanism of renoprotective effect of exercise training : Role of renal cytochrome P-450 metabolism of arachidonic acid

运动训练的肾脏保护作用机制：肾细胞色素 P-450 花生四烯酸代谢的作用

基本信息

批准号：
16500332
负责人：
ITO Osamu
金额：
$ 2.18万
依托单位：
Tohoku University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2004
资助国家：
日本
起止时间：
2004 至 2005
项目状态：
已结题

项目摘要

1.To clarify the mechanism of the renal-protective effects of chronic exercise, the effect of chronic exercise on the cytochrome P-450 (CYP) metabolism of arachidonic acid (AA) was determined. Wistar-Kyoto rats were separated to a control or an exercise group. After 8 weeks, the production of the metabolites of AA by kidney and liver microsomes was measured. In the kidney, exercise increased the production of 20-hydroxyeicosatetraenoic acid (20-HETE), whereas it did not affect the production of epoxyeicosatrienoic acids (EETs). In the liver, exercise did not affect the production of 20-HETE, whereas it decreased the production of EETs. The increased production of 20-HETE in the kidney may contribute to the renal-protective effects of chronic exercise.2.CYP4 family catalyze the ω-hydroxylation of AA. In rat, CYP4A was expressed in the proximal tubule, with lower expression in the preglomerular microvessel, glomerulus and thick ascending limb (TAL), but the expression was not detected in the collecting duct. In human, CYP4A and CYP4F were expressed in the proximal tubules, with lower expression in the TAL and collecting duct, but no expression in the glomerulus or renal vasculatures.3.The renal CYP metabolism of AA in vasopressin-deficient Brattleboro (BB) and control Long-Evans (LE) rats and the effects of a CYP inhibitor, 1-aminobenzotriazole (ABT) on renal function in these animals were compared. The production of 20-HETE by renal microsomes was significantly greater in BB rats than in LE rats. The expression of CYP4A proteins was higher in BB rats than LE rats. Chronic blockade of the formation of 20-HETE and EETs with ABT had little effects on renal function in LE rats. However, GFR and urine flow increased and urine osmolarity decreased in BB rats treated with ABT. These results suggest that the elevating formation of 20-HETE in the kidney may regulate GFR and water excretion in BB rats.

1.为了阐明长期运动的肾脏保护作用的机制，将Wistar-Kyoto大鼠分为对照组和对照组，测定了长期运动对花生四烯酸（AA）细胞色素P-450（CYP）代谢的影响。 8周后，测量了肾脏和肝脏微粒体产生的AA代谢物，运动增加了肾脏中20-羟基二十碳四烯酸的产生。（20-HETE），而它不影响环氧二十碳三烯酸（EET）的产生。在肝脏中，运动不影响 20-HETE 的产生，但它减少了 20-HETE 的产生。 2.CYP4家族催化AA的ω-羟基化在大鼠中，CYP4A在肾脏中表达。 CYP4A 和 CYP4F 在近曲小管中表达，在肾小球前微血管、肾小球和粗升肢 (TAL) 中表达较低，但在集合管中未检测到表达。 3.加压素缺乏的Brattleboro中AA的肾CYP代谢(BB) 和对照 Long-Evans (LE) 大鼠以及 CYP 抑制剂 1-氨基苯并三唑 (ABT) 对这些动物肾功能的影响进行了比较。 BB 大鼠的肾微粒体产生的 20-HETE 明显更高。 BB 大鼠的 CYP4A 蛋白表达高于 LE 大鼠，ABT 长期阻断 20-HETE 和 EET 的形成对肾功能影响不大。然而，用 ABT 治疗的 BB 大鼠中，GFR 和尿流量增加，尿渗透压降低。这些结果表明，肾脏中 20-HETE 形成的增加可能调节 BB 大鼠的 GFR 和水排泄。