The Water and Salt Research Center, University of Aarhus, Denmark.
Acta Physiol (Oxf). 2011 May;202(1):79-90. doi: 10.1111/j.1748-1716.2011.02257.x. Epub 2011 Mar 22.
Cisplatin (CP) induced acute renal failure (ARF) has previously been associated with decreased urinary prostaglandin E2 (PGE2) excretion and reduced aquaporin 2 (AQP2) expression in kidney collecting duct. In this study we examined the expression of cyclooxygenase (COX)-1 and -2 as well as AQP2 and the Na-K-2Cl cotransporter in kidneys from rats with CP induced ARF.
Rats were treated with either CP or saline and followed for 5 days. Kidneys were dissected into three zones and prepared for immunoblotting, quantitative polymerase chain reaction (QPCR) and immunohistochemistry. Renal content and urinary PGE2 excretion was measured.
Cisplatin treatment was associated with polyuria and a significant decreased creatinine clearance. Inner medullary PGE2 content and urinary PGE2 excretion was decreased in CP-treated rats. QPCR and semiquatitative immunoblotting demonstrated that CP treatment reduced COX-2, AQP2 and Na-K-2Cl cotransporter abundance in the different kidney zones, whereas no change in COX-1 was observed. Results were confirmed by immunohistochemistry.
Cyclooxygenase-2 expression is decreased in inner medulla and cortex. Consistent with this urinary PGE2 levels were reduced. These data suggest that downregulation of COX-2 is responsible for impaired de novo generation of vasodilatory prostaglandins which may play an important role for the CP induced renal vasoconstriction and development of nephropathy.
顺铂（CP）诱导的急性肾衰竭（ARF）以前与肾脏集合管中前列腺素 E2（PGE2）排泄减少和水通道蛋白 2（AQP2）表达降低有关。在这项研究中，我们检查了 CP 诱导的 ARF 大鼠肾脏中环氧化酶（COX）-1 和 -2 以及 AQP2 和 Na-K-2Cl 共转运蛋白的表达。
用 CP 或生理盐水处理大鼠，并在第 5 天进行随访。将肾脏分为三个区，并进行免疫印迹、定量聚合酶链反应（QPCR）和免疫组织化学分析。测量肾内容物和尿 PGE2 排泄量。
CP 处理与多尿和肌酐清除率显著降低有关。CP 处理大鼠的内髓质 PGE2 含量和尿 PGE2 排泄量减少。QPCR 和半定量免疫印迹显示 CP 处理降低了不同肾脏区域的 COX-2、AQP2 和 Na-K-2Cl 共转运蛋白的丰度，而 COX-1 没有变化。免疫组织化学结果得到了证实。
COX-2 在内髓质和皮质中的表达减少。与这一结果一致的是，尿 PGE2 水平降低。这些数据表明 COX-2 的下调导致新生成的血管扩张性前列腺素减少，这可能在 CP 诱导的肾脏血管收缩和肾病发展中起重要作用。
