L-carnitine alleviating cisplatin induced acute kidney injury through serum metabolomics analysis
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摘要: 目的 利用血清代谢组学探究顺铂诱导小鼠急性肾损伤的特异性变量,同时评价左卡尼汀的干预作用。 方法 将19只小鼠分为正常对照组、模型组和干预组,适应3 d后,对干预组给予左卡尼汀(400 mg/kg,ip)干预,2 d后给予模型组和干预组顺铂(20 mg/kg,ip)造模,每天称量各组小鼠的体质量,2 d后取小鼠血清进行LC-MS分析,结合模式识别分析各组间代谢组差异,并评价左卡尼汀的干预作用。 结果 代谢组学分析共鉴别28个差异代谢物,顺铂诱导的急性肾损伤主要涉及磷脂类、氨基酸类和脂肪酸类代谢途径的改变,而左卡尼汀有改善作用。 结论 左卡尼汀可改善顺铂诱导的急性肾损伤,其机制可能是通过调控色氨酸代谢、谷氨酸代谢和能量代谢,从而减缓急性肾损伤的疾病进程。Abstract: Objective To explore specific variables related to cisplatin induced acute kidney injury, serum metabonomics techniques were applied and simultaneously the value of intervention effects of L-carnitine were appraised. Methods 19 mice were divided into the normal control group, model group, and intervention group, After a three day accommodation period, the intervention group was given L-carnitine (400 mg/kg, ip). Two days later, cisplatin (20 mg/kg, ip) was given to the model and intervention groups. The body weight of every mouse in each group was measured daily. Two days after the serum sample of each mice was collected and analyzed by LC-MS, pattern recognition analysis of metabolomics differences among the groups, and the effectiveness of L-carnitine intervention were evaluated. Results A total of 28 metabolites were identified through serum metabolomics analysis. Our data shows that there is a possible mechanism that cisplatin induced AKI was mainly involved in changing phospholipids, amino acid and fatty acid metabolic pathways and L-carnitine mitigates the damage of acute kidney injury induced by cisplatin. Conclusion L-carnitinecan alleviates cisplatin induced acute kidney injury by regulating tryptophan metabolism, glutamate metabolism, and energy metabolism.
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Key words:
- L-carnitine /
- cisplatin /
- acute kidney injury /
- metabolomics
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[1] 朱晓红. 顺铂的不良反应及防护[J]. 药物与临床, 2001,16(2): 35-37. [2] 张立元, 朱振红, 王 敏, 等. NGAL预测和早期诊断顺铂所致急性肾损伤的研究[J]. 中华肿瘤防治杂志, 2013, 20 (14): 1113-1116. [3] 潘晶晶, 宣小燕, 张爱华, 等. 线粒体功能障碍参与顺铂诱导的小鼠急性肾损伤[J]. 中华肾脏病杂志, 2013,29(12): 914-919. [4] Zambrano S, Blanca AJ, Ruiz-Armenta MV, et al. L-carnitine attenuates the development of kidney fibrosis in hypertensive rats by upregulating PPAR-γ[J]. Am J Hypert, 2014,27(3): 460-470. [5] Liu Y, Yan S, Ji C, et al. Metabolomic changes and protective effect of L-carnitine in rat kidney ischemia/reperfusion injury[J]. Kidney Blood Press Res, 2012,35(5): 373-381. [6] Zgoda-Pols JR, Chowdhury S, Wirth M,et al. Metabolomics analysis reveals elevation of 3-indoxyl sulfate in plasma and brain during chemically-induced acute kidney injury in mice: investigation of nicotinic acid receptor agonists[J]. Toxicol Appl Pharmacol, 2011,255(1): 48-56. [7] Portilla D, Schnackenberg L, Beger RD. Metabolomics as an extension of proteomic analysis: study of acute kidney injury[J]. Semin Nephrol, 2007,27(6): 609-620. [8] Song X, Wang J, Wang P, et al. 1H NMR-based metabolomics approach to evaluate the effect of Xue-Fu-Zhu-Yu decoction on hyperlipidemia rats induced by high-fat diet[J]. J Pharm Biomed Anal, 2013,78-79: 202-210. [9] Wong M, Lodge JK. A metabolomic investigation of the effects of vitamin E supplementation in humans[J]. Nutr Metab (Lond), 2012,9(1): 110.
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