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首页> 外文学位 >Branched chain amino acid supplementation modulates the effect of inflammatory mediators on the function of a hepatoma cell line.
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Branched chain amino acid supplementation modulates the effect of inflammatory mediators on the function of a hepatoma cell line.

机译：支链氨基酸的补充调节了炎症介质对肝癌细胞系功能的影响。

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摘要

Severe trauma injuries often lead to a prolonged inflammatory response associated with metabolic abnormalities. These abnormalities lead to persistent skeletal muscle proteolysis and rapid loss of lean body mass, which may lead to multiple organ dysfunction and death. The liver plays an important role in this systemic response to injury by modulating the inflammatory processes, immune functions, and metabolic pathways. The acute phase of the response is characterized by the release of inflammatory mediators, including proinflammatory cytokines and reactive oxygen species (ROS), as well as a change in the protein secretion pattern and increased amino acid utilization by the liver. When these changes persist for long periods of time, they likely contribute to the body’s negative nitrogen balance as well as loss of lean body mass (LBM). Among all proteins secreted by the liver, albumin is the most abundant one and its secretion rate significantly decreases in inflammatory states, and results in a lower circulating concentration in patients. Albumin provides the critical colloid osmotic pressure to regulate the passage of water and diffusible solutes through the capillaries. Increased utilization of amino acids in trauma is thought to be important for defense against diseases; however, it reduces body stores of proteins and free amino acids to supply amino acid needs for tissue repair, acute phase protein production, and gluconeogenesis. Nutritional supplementation is currently being used to alleviate endogenous nitrogen depletion and to maximize protein synthesis for optimal wound healing and immune function. Among nutritional supplements, there has been increased interest in using branched chain amino acids (BCAAs), and clinical studies suggest that BCAAs can enhance liver function in inflammatory states. The mechanism whereby BCAAs impact the liver function during inflammation is unclear. The purpose of this research is to investigate the effect of proinflammatory mediators (more specifically the cytokines interleukin-1ß & interleukin-6) and reactive oxygen species H2O2, and BCAAs on a cell culture model of liver consisting of HepG2/C3A hepatoma cells. It was found that these mediators reversibly suppressed albumin and urea production in a dose-dependent manner, and also decreased the amount of the intracellular antioxidant reduced glutathione. BCAA supplementation mitigated the effect of these inflammatory mediators; however, this effect was maximized at a relatively low concentration of BCAAs, above which no further benefit was observed. Therefore, BCAAs are potentially beneficial to support liver function during inflammation.
机译：严重的外伤经常导致与代谢异常相关的长时间炎症反应。这些异常导致持续的骨骼肌蛋白水解和瘦体重的快速丧失，这可能导致多器官功能障碍和死亡。肝脏通过调节炎症过程，免疫功能和代谢途径，在对损伤的全身反应中起重要作用。反应的急性期的特征在于炎症介质的释放，包括促炎细胞因子和活性氧（ROS），以及蛋白质分泌方式的改变和肝脏对氨基酸的利用增加。如果这些变化持续很长时间，则可能会导致人体负氮平衡以及瘦体重（LBM）下降。在所有由肝脏分泌的蛋白质中，白蛋白是最丰富的一种，在炎症状态下白蛋白的分泌率显着降低，并导致患者体内的循环浓度降低。白蛋白提供临界的胶体渗透压，以调节水和可扩散溶质通过毛细管的通道。人们认为增加创伤中氨基酸的利用对防御疾病很重要。但是，它减少了蛋白质和游离氨基酸在人体中的存储，从而满足了组织修复，急性期蛋白质生产和糖异生的氨基酸需求。目前，营养补充已被用于减轻内源性氮耗竭并最大化蛋白质合成，以实现最佳的伤口愈合和免疫功能。在营养补品中，人们对使用支链氨基酸（BCAAs）的兴趣日益增加，临床研究表明，BCAAs可以增强炎症状态下的肝功能。 BCAA在炎症过程中影响肝功能的机制尚不清楚。本研究的目的是研究促炎性介质（更具体地讲，白细胞介素-1ß和白介素-6的细胞因子），活性氧H2O2和BCAA对由HepG2 / C3A肝癌细胞组成的肝脏细胞培养模型的影响。发现这些介质以剂量依赖的方式可逆地抑制白蛋白和尿素的产生，并且还减少了细胞内抗氧化剂还原的谷胱甘肽的量。补充BCAA可减轻这些炎症介质的作用。但是，在相对较低的BCAA浓度下，这种作用会最大化，超过此浓度则未观察到进一步的益处。因此，BCAAs在炎症过程中可能有益于支持肝功能。

著录项

  • 作者

    Hashemi, Sharareh.;

  • 作者单位

    Rutgers The State University of New Jersey - New Brunswick and University of Medicine and Dentistry of New Jersey.;

  • 授予单位 Rutgers The State University of New Jersey - New Brunswick and University of Medicine and Dentistry of New Jersey.;
  • 学科 Biology Cell.;Engineering Biomedical.
  • 学位 M.S.
  • 年度 2013
  • 页码 101 p.
  • 总页数 101
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

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