Yoshida Takumi, Kurella Manjula, Beato Francisca, Min Hyunsuk, Ingelfinger Julie R, Stears Robin L, Swinford Rita D, Gullans Steven R, Tang Shiow-Shih
Pediatric Nephrology Unit, Massachusetts General Hospital, Renal Division, Department of Medicine, Brigham & Women's Hospital, Harvard Medical School, Boston, Massachusetts 02114, USA.
Kidney Int. 2002 May;61(5):1646-54. doi: 10.1046/j.1523-1755.2002.00341.x.
Although acute renal failure (ARF) is a relatively common disorder with major morbidity and mortality, its molecular basis remains incompletely defined. The present study examined global gene expression in the well-characterized ischemia-reperfusion model of ARF using DNA microarray technology.
Male Wistar rats underwent bilateral renal ischemia (30 min) or sham operation, followed by reperfusion for 1, 2, 3 or 4 days. Plasma creatinine increased approximately fivefold over baseline, peaking on day 1. Renal total RNA was used to probe cDNA microarrays.
Alterations in expression of 18 genes were identified by microarray analysis. Nine genes were up-regulated (ADAM2, HO-1, UCP-2, and thymosin beta4 in the early phase and clusterin, vanin1, fibronectin, heat-responsive protein 12 and FK506 binding protein in the established phase), whereas another nine were down-regulated (glutamine synthetase, cytochrome p450 IId6, and cyp 2d9 in the early phase and cyp 4a14, Xist gene, PPARgamma, alpha-albumin, uromodulin, and ADH B2 in the established phase). The identities of these 18 genes were sequence-verified. Changes in gene expression of ADAM2, cyp2d6, fibronectin, HO-1 and PPARgamma were confirmed by quantitative real-time polymerase chain reaction (PCR). ADAM2, cyp2d6, and PPARgamma have not previously been known to be involved in ARF.
Using DNA microarray technology, we identified changes in expression of 18 genes during renal ischemia-reperfusion injury in the rat. We confirmed changes in five genes (fibronectin, ADAM2, cyp 2d6, HO-1 and PPARgamma) by quantitative real-time PCR. Several genes, not previously been identified as playing a role in ischemic ARF, may have importance in this disease.
尽管急性肾衰竭（ARF）是一种发病率和死亡率较高的相对常见的病症，但其分子基础仍未完全明确。本研究使用DNA微阵列技术检测了特征明确的ARF缺血再灌注模型中的整体基因表达情况。
雄性Wistar大鼠接受双侧肾脏缺血（30分钟）或假手术，随后再灌注1、2、3或4天。血浆肌酐比基线水平升高约五倍，在第1天达到峰值。肾脏总RNA用于探测cDNA微阵列。
通过微阵列分析鉴定出18个基因的表达发生改变。9个基因上调（早期阶段的ADAM2、HO-1、UCP-2和胸腺素β4，以及已确立阶段的簇集蛋白、血管生成素1、纤连蛋白、热反应蛋白12和FK506结合蛋白），而另外9个基因下调（早期阶段的谷氨酰胺合成酶、细胞色素P450 IId6和cyp 2d9，以及已确立阶段的cyp 4a14、Xist基因、PPARγ、α-白蛋白、尿调节蛋白和抗利尿激素B2）。这18个基因的身份经序列验证。通过定量实时聚合酶链反应（PCR）证实了ADAM2、cyp2d6、纤连蛋白、HO-1和PPARγ基因表达的变化。ADAM2、cyp2d6和PPARγ以前未知与ARF有关。
使用DNA微阵列技术，我们鉴定出大鼠肾脏缺血再灌注损伤期间18个基因的表达变化。我们通过定量实时PCR证实了5个基因（纤连蛋白、ADAM2、cyp 2d6、HO-1和PPARγ）的变化。几个以前未被确定在缺血性ARF中起作用的基因，可能在这种疾病中具有重要意义。
