首页> 外文学位 >Role of Hyperhomocysteinemia in the Regulation of Oxidative Stress and Inflammatory Responses in the Kidney: Protective Effect of Folic Acid Supplementation.
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Role of Hyperhomocysteinemia in the Regulation of Oxidative Stress and Inflammatory Responses in the Kidney: Protective Effect of Folic Acid Supplementation.

机译:高同型半胱氨酸血症在肾脏氧化应激和炎症反应调节中的作用:补充叶酸的保护作用。

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摘要

Hyperhomocysteinemia, a condition of elevated blood homocysteine (Hcy) level, is an independent risk factor for cardiovascular disease. Folic acid supplementation can effectively reduce blood Hcy levels. Recent studies have demonstrated that hyperhomocysteinemia is also associated with kidney disease. However, the underlying mechanisms remain unclear. The overall objective of the study was to investigate the biochemical and molecular mechanisms of Hcy-induced kidney injury and the effect of folic acid supplementation on Hcy-induced kidney injury.;Hyperhomocysteinemia was induced in Sprague-Dawley rats by feeding a high-methionine diet for 12 weeks. An elevation of serum total Hcy level was observed in hyperhomocysteinemic rats. Hyperhomocysteinemia-induced superoxide anion production via nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activation resulted in oxidative stress in the kidney. Reduction of oxidative stress by inhibiting superoxide anion production effectively ameliorated hyperhomocysteinemia-induced kidney injury.;Inflammatory responses such as increased chemokine expression have been implicated as one of the mechanisms of kidney disease. Monocyte chemoattractant protein-1 (MCP-1) is a potent chemokine that is involved in the inflammatory response in kidney disease. Nuclear factor-kappa B (NF-kappaB) plays an important role in upregulation of MCP-1 expression. We investigated the effect of hyperhomocysteinemia on MCP-1 expression and the molecular mechanism responsible for such an effect in rat kidneys as well as in human kidney proximal tubular cells.
机译:高同型半胱氨酸血症是血液高半胱氨酸(Hcy)水平升高的一种情况,是心血管疾病的独立危险因素。叶酸的补充可以有效降低血液中Hcy水平。最近的研究表明,高同型半胱氨酸血症也与肾脏疾病有关。但是,其潜在机制仍不清楚。本研究的总体目标是研究Hcy引起的肾脏损伤的生化和分子机制以及叶酸补充对Hcy引起的肾脏损伤的影响。;高蛋氨酸饮食喂养Sprague-Dawley大鼠高同型半胱氨酸血症持续12周。高同型半胱氨酸血症大鼠血清总Hcy水平升高。高同型半胱氨酸血症诱导的烟酰胺腺嘌呤二核苷酸磷酸(NADPH)氧化酶活化导致超氧阴离子的产生,导致肾脏氧化应激。通过抑制超氧阴离子的产生来降低氧化应激可有效改善高同型半胱氨酸血症引起的肾脏损伤。炎症反应,例如趋化因子表达的增加是肾脏疾病的机制之一。单核细胞趋化蛋白-1(MCP-1)是一种有效的趋化因子,参与肾脏疾病的炎症反应。核因子κB(NF-κB)在MCP-1表达上调中起重要作用。我们调查了高同型半胱氨酸血症对MCP-1表达的影响以及在大鼠肾脏以及人肾近端肾小管细胞中引起这种作用的分子机制。

著录项

  • 作者

    Hwang, Sun-Young.;

  • 作者单位

    University of Manitoba (Canada).;

  • 授予单位 University of Manitoba (Canada).;
  • 学科 Nutrition.;Biochemistry.;Molecular physics.
  • 学位 Ph.D.
  • 年度 2012
  • 页码 247 p.
  • 总页数 247
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

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