Department of Biochemistry and Molecular Biology, New York Medical College, Valhalla, New York 10595, USA.
J Urol. 2011 Dec;186(6):2448-54. doi: 10.1016/j.juro.2011.08.010. Epub 2011 Oct 21.
Extended warm ischemia during partial nephrectomy can lead to considerable renal injury. Using a rat model of renal ischemia we examined the ability of a unique renoprotective cocktail to ameliorate warm ischemia-reperfusion injury.
A warm renal ischemia model was developed using 60 Sprague-Dawley® rats. The left renal artery was clamped for 40 minutes, followed by 48 hours of reperfusion. A renoprotective cocktail of a mixture of specific growth factors, mitochondria protecting biochemicals and Manganese-Porphyrin (MnTnHex-2-PyP(5+)) was given intramuscularly at -24, 0 and 24 hours after surgery. At 48 hours the 2 kidneys were harvested and examined with hematoxylin and eosin, and periodic acid-Schiff stains. Protein and gene expression were also analyzed to determine ischemia markers and the antioxidant response.
Compared to ischemic controls, kidneys treated with the renoprotective cocktail showed significant reversal of morphological changes and a significant decrease in the specific ischemic markers lipocalin-2, mucin-1 and galectin-3. Quantitative reverse transcriptase-polymerase chain reaction revealed up-regulation of several antioxidant genes in treated animals.
According to histopathological and several molecular measures our unique renoprotective cocktail mitigated ischemia-reperfusion injury.
部分肾切除术期间的延长热缺血可导致相当大的肾损伤。我们使用大鼠肾缺血模型研究了一种独特的肾保护鸡尾酒在改善热缺血再灌注损伤方面的能力。
使用 60 只 Sprague-Dawley®大鼠建立了热肾缺血模型。夹闭左肾动脉 40 分钟，然后再灌注 48 小时。在手术后 -24、0 和 24 小时，通过肌肉内给予特定生长因子、线粒体保护生化物质和锰卟啉（MnTnHex-2-PyP(5+））的肾保护鸡尾酒。48 小时后，收获 2 个肾脏，并进行苏木精和伊红以及过碘酸希夫染色检查。还分析了蛋白质和基因表达，以确定缺血标志物和抗氧化反应。
与缺血对照相比，用肾保护鸡尾酒治疗的肾脏显示出形态变化的显著逆转，并且特定的缺血标志物脂联素-2、粘蛋白-1 和半乳糖凝集素-3 的水平显著降低。定量逆转录聚合酶链反应显示，治疗动物中几种抗氧化基因的上调。
根据组织病理学和几种分子测量，我们独特的肾保护鸡尾酒减轻了缺血再灌注损伤。
