Regulation in expression of anti-oxidative enzymes in progressive renal injury

醛糖还原酶(AR)和醛还原酶(ALR)是醛酮还原酶超家族的成员，参与了多种羰基化合物的还原。然而，这些还原酶在肾脏疾病中的作用尚不清楚。本研究检测了大鼠肾次全切除后1、2、4、10周大鼠残肾组织中AR和ALR的表达。免疫印迹分析和免疫组织化学染色检测肾组织AR和ALR的表达。在残肾中，AR在2周时表达增加，并且随着肾功能衰竭的进展，AR的表达呈时间依赖性增加。相反，在假手术组，AR的表达没有变化。有趣的是，直到术后10周，ALR在残肾和假手术肾中的表达都没有变化。免疫组织化学检测显示，假手术组大鼠远端肾小管上皮细胞、Henle氏环和足细胞中AR表达较弱。然而，在残肾中，除肾小球内皮细胞外，肾小球内皮细胞的AR表达增加。在假手术组和肾切除组，ALR在近曲小管均有表达。肾切除组大鼠血清活性羰基化合物水平高于假手术组。我们的结果表明，AR和ALR对肾质量减少所致的肾损伤表现出不同的反应。提示AR可能在保护肾脏免受肾功能衰竭所致的羰基应激损伤中起重要作用。此外，在残肾中还检测到硫氧还蛋白还原酶和过氧化还蛋白等其他抗氧化酶的表达。

Aldose reductase (AR) and aldehyde reductase (ALR) are members of the aldo-keto reductase superfamily, and participate in the reduction of a wide range of carbonyl compounds. However, the roles of these reductases in the renal disease are unclear. In this study, we examined the expressions of AR and ALR in the rat remnant kidney at 1, 2, 4 and 10 weeks after subtotal nephrectomy. Expressions of AR and ALR are evaluated by Western blot analysis and immunostaining of renal tissue. In remnant kidney increased AR expression was detected at 2 weeks and AR expression was time-dependently increased during the progression of renal failure. In contrast, in sham-operated kidney AR expression was unchanged. Interestingly, ALR expressions were changed neither in remnant kidney nor in sham-operated kidney up to 10 weeks after surgery. Immunohistochemical examination revealed that in sham-operated rats AR expression was weakly detected in distal tubular epithelial cells, Henle's loop and podocytes. However, in remnant kidney increased AR expression was detected in glomerular endothelial cells in addition to them. ALR expression was observed in proximal tubules in both sham-operated and nephrectomized rats. The serum levels of reactive carbonyl compounds were higher in nephrectomized rats than in sham-operated rats. Our results indicate that AR and ALR show different responses to renal injury induced by renal mass reduction. This suggested that AR may play an important role to protect kidneys from carbonyl stress caused by renal failure. Furthermore, the expression of other anti-oxidative enzymes including thioredoxin reductase and peroxiredoxins were also detected in remnant kidney.