Department of Anesthesiology and Intensive Care Medicine, Oita University, Faculty of Medicine, Oita, Japan.
J Surg Res. 2012 May 15;174(2):352-8. doi: 10.1016/j.jss.2011.01.011. Epub 2011 Feb 3.
Ischemia-reperfusion (I/R) occurs frequently in a variety of clinical settings, such as renal transplantation. In addition, I/R is a major cause of acute kidney injury (AKI). A recent study has reported that reactive oxygen species (ROS) are important mediators of AKI, suggesting that reducing ROS generation may prevent renal injury. The present study evaluated the ability of DHL-HisZn, a new α-lipoic acid derivative, to inhibit ROS generation and prevent renal I/R injury in rats.
Rats received an intravenous infusion of DHL-HisZn or saline, and then underwent experimentally induced renal I/R injury or sham treatment. Rats were sacrificed after 60 min of ischemia and 24 h of reperfusion. To evaluate the renal protective effects of DHL-HisZn, serum blood urea nitrogen (BUN) and creatinine (Cre) concentrations were determined, kidneys were histologically assessed, and malondialdehyde (MDA), a biomarker of oxidative stress, was evaluated. In addition, antimycin A (AMA)-stimulated RAW264.7 cells were treated with DHL-HisZn to assess its antioxidant effects in vitro.
DHL-HisZn treatment attenuated I/R-induced histologic alterations, reduced serum levels of serum BUN and Cre, and decreased MDA levels in the kidneys of rats with renal I/R injury. Furthermore, DHL-HisZn decreased ROS levels in AMA-stimulated RAW264.7 cells.
Our in vitro and in vivo findings suggest that DHL-HisZn may have therapeutic potential against various human I/R conditions.
缺血再灌注（I/R）在多种临床情况下经常发生，例如肾移植。此外，I/R 是急性肾损伤（AKI）的主要原因。最近的一项研究报告称，活性氧（ROS）是 AKI 的重要介质，这表明减少 ROS 的产生可能预防肾损伤。本研究评估了新型 α-硫辛酸衍生物 DHL-HisZn 抑制 ROS 生成并预防大鼠肾 I/R 损伤的能力。
大鼠接受 DHL-HisZn 或生理盐水的静脉输注，然后进行实验性诱导的肾 I/R 损伤或假处理。缺血 60 分钟和再灌注 24 小时后处死大鼠。为了评估 DHL-HisZn 的肾保护作用，测定血清血尿素氮（BUN）和肌酐（Cre）浓度，对肾脏进行组织学评估，并评估丙二醛（MDA），一种氧化应激的生物标志物。此外，用 DHL-HisZn 处理 antimycin A（AMA）刺激的 RAW264.7 细胞，以评估其在体外的抗氧化作用。
DHL-HisZn 治疗减轻了 I/R 引起的组织学改变，降低了肾 I/R 损伤大鼠血清 BUN 和 Cre 水平，并降低了肾脏 MDA 水平。此外，DHL-HisZn 降低了 AMA 刺激的 RAW264.7 细胞中的 ROS 水平。
我们的体内外研究结果表明，DHL-HisZn 可能对各种人类 I/R 情况具有治疗潜力。
