Metabolomic Changes and Protective Effect of L-Carnitine in Rat Kidney Ischemia/Reperfusion Injury
Metabolomic Changes and Protective Effect of L-Carnitine in Rat Kidney Ischemia/Reperfusion Injury
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DOI：
10.1159/000336171
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发表时间：
2012-01-01
影响因子：
2.8
通讯作者：
Mei, Changlin
中科院分区：
文献类型：
--
作者：
Liu, Ye;Yan, Shikai;Mei, Changlin
工作背景：尽管对急性肾损伤（阿基）的发病机制和治疗已取得了很大进展，但其发病率高、预后差。本研究旨在进一步了解缺血/再灌注（I/R）诱导阿基的代谢组学变化及左旋卡尼汀对阿基的保护作用。研究方法：对照组、I/R组和L-卡尼汀预处理组于不同时间点采集肾组织和血清标本。采用高效液相色谱-质谱联用技术研究大鼠肾I/R模型中阿基的特点及L-卡尼汀的保护作用。测定抗氧化酶活性和磷脂酶A（2）活性以验证代谢结果。结果如下：作为肾I/R损伤的结果的内源性代谢产物的模式的变化很容易检测到早在2小时后再灌注，并早于血尿素氮和血清肌酐的增加。通过MSn分析发现并鉴定了28种差异内源性代谢产物。与对照组相比，I/R损伤后，溶血磷脂、游离脂肪酸和硝基酪氨酸显著增加，而肉毒碱和乙酰肉毒碱显著降低。肾I/R损伤大鼠磷脂酶A2活性和丙二醛水平升高，超氧化物歧化酶活性降低。再灌注前30 min给予L-卡尼汀可显著减轻I/R诱导的代谢组学变化。结论：I/R诱导的阿基可通过代谢组学研究以氧化应激和脂质代谢变化为特征，再灌注前30 min给予L-肉碱对I/R诱导的阿基具有保护作用。版权所有（c）2012 S. Karger AG，巴塞尔
Background: Although great progress has been made in the pathogenesis and treatment of acute kidney injury (AKI), it still has high incidence and poor prognosis. The present study was performed in order to further understand the metabolomic changes of ischemia/reperfusion (I/R)-induced AKI and the protective effect of L-carnitine on AKI. Methods: Kidney tissues and serum samples were collected at different time points from three groups of rats including control group, I/R group and L-carnitine-pretreated group. High-performance liquid chromatography coupled with mass spectrometry-based metabolomics approach was applied to investigate the characteristic of I/R-induced AKI and the protective effects of L-carnitine in rat kidney I/R model. Antioxidant enzymatic activity and phospholipase A(2) activity were determined to validate the metabolic outcomes. Results: Changes in the pattern of endogenous metabolites as a result of kidney I/R injury were readily detected as early as 2 h after reperfusion, and earlier than the increase in blood urea nitrogen and serum creatinine. Twenty-eight differential endogenous metabolites were discovered and structurally identified by MSn analysis. After I/R injury, lysophospholipids, free fatty acids and nitrotyrosine significantly increased, while carnitine and acetyl-carnitine significantly decreased compared to control. Phospholipase A(2) activity and malondialdehyde level also increased, while superoxide dismutase activity decreased in kidney I/R injury rats. Treatment of L-carnitine 30 min prior to reperfusion significantly relieved I/R-induced metabolomic changes. Conclusion: I/R-induced AKI could be characterized by oxidative stress and changes in lipid metabolism through metabolomic investigation, and L-carnitine treatment 30 min before reperfusion had protective effects against I/R-induced AKI. Copyright (c) 2012 S. Karger AG, Basel