Department of Food Science and Experimental Nutrition, Faculty of Pharmaceutical Sciences, University of São Paulo, São Paulo, Brazil; School of Biomedical Sciences, CHIRI Biosciences Research Precinct, Faculty of Health Sciences, Curtin University, Perth, Western Australia.
Department of Physiology, Institute of Basic Health Sciences, Federal University of Rio Grande do Sul, Rua Sarmento Leite, Porto Alegre, Brazil.
Nutrition. 2014 May;30(5):602-11. doi: 10.1016/j.nut.2013.10.019. Epub 2013 Oct 31.
The aim of the present study was to determine the effects of oral supplementation with L-glutamine plus L-alanine (GLN+ALA), both in the free form and L-alanyl-L-glutamine dipeptide (DIP) in endotoxemic mice.
B6.129 F2/J mice were subjected to endotoxemia (Escherichia coli lipopolysaccharide [LPS], 5 mg/kg, LPS group) and orally supplemented for 48 h with either L-glutamine (1 g/kg) plus L-alanine (0.61 g/kg) (GLN+ALA-LPS group) or 1.49 g/kg DIP (DIP-LPS group). Plasma glutamine, cytokines, and lymphocyte proliferation were measured. Liver and skeletal muscle glutamine, glutathione (GSH), oxidized GSH (GSSG), tissue lipoperoxidation (TBARS), and nuclear factor (NF)-κB-interleukin-1 receptor-associated kinase 1 (IRAK1)-Myeloid differentiation primary response gene 88 pathway also were determined.
Endotoxemia depleted plasma (by 71%), muscle (by 44%), and liver (by 49%) glutamine concentrations (relative to the control group), which were restored in both GLN+ALA-LPS and DIP-LPS groups (P < 0.05). Supplemented groups reestablished GSH content, intracellular redox status (GSSG/GSH ratio), and TBARS concentration in muscle and liver (P < 0.05). T- and B-lymphocyte proliferation increased in supplemented groups compared with controls and LPS group (P < 0.05). Tumor necrosis factor-α, interleukin (IL)-6, IL-1 β, and IL-10 increased in LPS group but were attenuated by the supplements (P < 0.05). Endotoxemic mice exhibited higher muscle gene expression of components of the NF-κB pathway, with the phosphorylation of IκB kinase-α/β. These returned to basal levels (relative to the control group) in both GLN+ALA-LPS and DIP-LPS groups (P < 0.05). Higher mRNA of IRAK1 and MyD88 were observed in muscle of LPS group compared with the control and supplemented groups (P < 0.05).
Oral supplementations with GLN+ALA or DIP are effective in attenuating oxidative stress and the proinflammatory responses induced by endotoxemia in mice.
本研究旨在确定口服补充 L-谷氨酰胺加 L-丙氨酸（GLN+ALA），无论是游离形式还是 L-丙氨酰-L-谷氨酰胺二肽（DIP），对内毒素血症小鼠的影响。
B6.129 F2/J 小鼠接受内毒素血症（大肠杆菌脂多糖 [LPS]，5mg/kg，LPS 组），并在 48 小时内口服补充 L-谷氨酰胺（1g/kg）加 L-丙氨酸（0.61g/kg）（GLN+ALA-LPS 组）或 1.49g/kg DIP（DIP-LPS 组）。测量血浆谷氨酰胺、细胞因子和淋巴细胞增殖。还测定了肝和骨骼肌谷氨酰胺、谷胱甘肽（GSH）、氧化 GSH（GSSG）、组织脂质过氧化（TBARS）和核因子（NF）-κB-白细胞介素-1 受体相关激酶 1（IRAK1）-髓样分化初级反应基因 88 途径。
内毒素血症使血浆（减少 71%）、肌肉（减少 44%）和肝脏（减少 49%）中的谷氨酰胺浓度降低（与对照组相比），这在 GLN+ALA-LPS 和 DIP-LPS 组中都得到了恢复（P <0.05）。补充组恢复了肌肉和肝脏中的 GSH 含量、细胞内氧化还原状态（GSSG/GSH 比值）和 TBARS 浓度（P <0.05）。与对照组和 LPS 组相比，T 和 B 淋巴细胞增殖在补充组中增加（P <0.05）。肿瘤坏死因子-α、白细胞介素（IL）-6、IL-1β和 IL-10 在 LPS 组中增加，但被补充剂减弱（P <0.05）。内毒素血症小鼠的 NF-κB 途径组成部分的肌肉基因表达增加，IκB 激酶-α/β磷酸化。在 GLN+ALA-LPS 和 DIP-LPS 组中，这些基因表达水平（与对照组相比）恢复到基础水平（P <0.05）。与对照组和补充组相比，LPS 组肌肉中 IRAK1 和 MyD88 的 mRNA 表达更高（P <0.05）。
口服补充 GLN+ALA 或 DIP 可有效减轻内毒素血症引起的氧化应激和促炎反应。
