Transcriptional Profile of Genes Involved in Oxidative Stress and Antioxidant Defense in a Dietary Murine Model of Steatohepatitis
Transcriptional Profile of Genes Involved in Oxidative Stress and Antioxidant Defense in a Dietary Murine Model of Steatohepatitis
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DOI：
10.1089/ars.2010.3815
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发表时间：
2011-07-15
影响因子：
6.6
通讯作者：
Feldstein, Ariel E.
中科院分区：
文献类型：
--
作者：
Gornicka, Agnieszka;Morris-Stiff, Gareth;Feldstein, Ariel E.
氧化应激是非酒精性脂肪性肝炎（NASH）疾病进展的核心异常。然而，导致体内氧化损伤的相关途径仍然知之甚少。在这里，我们探讨了基因表达模式相关的氧化应激，抗氧化防御和活性氧代谢的饮食小鼠模型NASH。将C57 BL/6小鼠置于甲硫氨酸和胆碱缺乏（MCD）或对照（CTL）饲料中6周。通过生化和组织学指标监测肝脏氧化损伤和NASH的发展。采用实时荧光定量PCR技术对两组小鼠肝脏中84个氧化应激相关基因进行分析。喂食MCD饲料的小鼠显示ALT升高、NASH组织学特征和氧化性肝损伤，4-羟基壬烯醛和3-硝基酪氨酸升高。在所分析的基因中，GPx家族的上调最为显著，而SCD 1的下调最为显著。其他显著上调的基因包括Fmo 2和peroxiredoxins，而下调的基因包括过氧化氢酶和Serpinb 1b。我们的数据表明，氧化应激相关基因在饮食诱导的NASH小鼠的肝脏中差异表达。这些发现对NASH的发病机制和这种疾病患者的新治疗策略的发展具有重要意义。抗氧化剂。红牛信号15，437-445。
Oxidative stress is a core abnormality responsible for disease progression in nonalcoholic steatohepatitis (NASH). However, the relevant pathways that contribute to oxidative damage in vivo remain poorly understood. Here we explore the gene-expression patterns related to oxidative stress, antioxidant defense, and reactive oxygen metabolism in an established dietary murine model of NASH. C57BL/6 mice were placed on either a methionine- and choline-deficient (MCD) or a control (CTL) diet for 6 weeks. Hepatic oxidative damage and the development of NASH were monitored by biochemical and histologic indices. Analysis of 84 oxidative stress related genes was performed by real-time reverse transcription polymerase chain reaction (PCR) in the livers of the two groups of mice. Mice on the MCD diet showed increased ALT, histologic features of NASH, and oxidative liver damage with increases in 4-hydroxynonenal and 3-nitrotyrosine. Of the genes analyzed, the GPx family were most significantly upregulated, whereas SCD1 was most significantly downregulated. Other genes that were significantly upregulated included Fmo2 and peroxiredoxins, whereas genes downregulated included Catalase and Serpinb1b. Our data demonstrate that oxidative stress related genes are differentially expressed in the livers of mice with diet-induced NASH. These findings have important implications for NASH pathogenesis and the development of novel therapeutic strategies for patients with this condition. Antioxid. Red ox Signal. 15, 437-445.