Zhang Yunchang, Jia Hai, Jin Yuhang, Liu Ning, Chen Jingqing, Yang Ying, Dai Zhaolai, Wang Chao, Wu Guoyao, Wu Zhenlong
State Key Laboratory of Animal Nutrition, Department of Animal Nutrition and Feed Science, China Agricultural University, Beijing 100193, China.
State Key Laboratory of Agrobiotechnology, College of Biological Sciences, China Agricultural University, Beijing 100193, China.
J Nutr. 2020 May 1;150(5):1116-1125. doi: 10.1093/jn/nxaa036.
BACKGROUND: Liver dysfunction impairs immunological homeostasis. Glycine (Gly) has been reported to have antioxidative and anti-inflammatory effects and to regulate apoptosis in various models. OBJECTIVES: The aim of the present study was to determine whether Gly could attenuate LPS-induced liver injury. METHODS: In Experiment 1, 48 6-week-old male C57BL/6 mice were randomly assigned into one of 4 groups: CON (control), GLY [orally administered Gly, 5 g · kg body weight (BW)-1 · d-1 for 6 d], LPS (5 mg/kg BW, intraperitoneally administered), and GLY + LPS (Gly supplementation, and on day 7 LPS treatment). In Experiment 2, mice were untreated, pretreated with Gly as above, or pretreated with Gly + l-buthionine sulfoximine (BSO) (0.5 g/kg BW, intraperitoneally administered every other day) for 6 d. On day 7, mice were injected with LPS as above. Histological alterations, activities of antioxidative enzymes, apoptosis, and immune cell infiltration were analyzed. RESULTS: In Experiment 1, compared with CON, LPS administration resulted in increased karyolysis and karyopyknosis in the liver by 8- to 10-fold, enhanced serum activities of alanine transaminase (ALT), aspartate transaminase (AST), and lactate dehydrogenase (LDH) by 1- to 1.8-fold, and increased hepatic apoptosis by 5.5-fold. Furthermore, LPS exposure resulted in increased infiltration of macrophages and neutrophils in the liver by 3.2- to 7.5-fold, elevated hepatic concentrations of malondialdehyde and hydrogen peroxide (H2O2), and elevated myeloperoxidase (MPO) activity by 1.5- to 6.3-fold. In Experiment 2, compared with the LPS group, mice in the GLY + LPS group had fewer histological alterations (68.5%-75.9%); lower serum ALT, AST, and LDH activities (24.3%-64.7%); and lower hepatic malondialdehyde and H2O2 concentrations (46.1%-80.2%), lower MPO activity (39.2%), immune cell infiltration (52.3%-85.3%), and apoptosis (69.6%), which were abrogated by BSO. Compared with the GLY + LPS group, mice in the GLY + BSO + LPS group had lower hepatic activities of catalase, superoxide dismutase, and glutathione peroxidase by 33.5%-48.5%; increased activation of NF-κB by 2.3-fold; and impaired nuclear factor (erythroid-derived 2)-like 2 signaling by 38.9%. CONCLUSIONS: Gly is a functional amino acid with an ability to protect the liver against LPS-induced injury in mice.
背景：肝功能障碍会损害免疫稳态。据报道，甘氨酸（Gly）在多种模型中具有抗氧化和抗炎作用，并能调节细胞凋亡。 目的：本研究旨在确定甘氨酸是否能减轻脂多糖（LPS）诱导的肝损伤。 方法：在实验1中，将48只6周龄雄性C57BL/6小鼠随机分为4组之一：对照组（CON）、GLY组（口服甘氨酸，5 g·kg体重（BW）-1·d-1，共6天）、LPS组（5 mg/kg BW，腹腔注射）和GLY + LPS组（补充甘氨酸，并在第7天进行LPS处理）。在实验2中，小鼠不进行处理、按上述方法用甘氨酸预处理或用甘氨酸 + L-丁硫氨酸亚砜胺（BSO）（0.5 g/kg BW，每隔一天腹腔注射）预处理6天。在第7天，小鼠按上述方法注射LPS。分析组织学改变、抗氧化酶活性、细胞凋亡和免疫细胞浸润情况。 结果：在实验1中，与CON组相比，给予LPS导致肝脏中的核溶解和核固缩增加8至10倍，血清丙氨酸转氨酶（ALT）、天冬氨酸转氨酶（AST）和乳酸脱氢酶（LDH）活性增强1至1.8倍，肝脏细胞凋亡增加5.5倍。此外，暴露于LPS导致肝脏中巨噬细胞和中性粒细胞浸润增加3.2至7.5倍，肝脏丙二醛和过氧化氢（H2O2）浓度升高，髓过氧化物酶（MPO）活性升高1.5至6.3倍。在实验2中，与LPS组相比，GLY + LPS组小鼠的组织学改变较少（68.5%-75.9%）；血清ALT、AST和LDH活性较低（2部4.3%-64.7%）；肝脏丙二醛和H2O2浓度较低（46.1%-80.2%），MPO活性较低（39.2%），免疫细胞浸润较少（52.3%-85.3%），细胞凋亡较少（69.6%），而BSO可消除这些作用。与GLY + LPS组相比，GLY + BSO + LPS组小鼠肝脏中的过氧化氢酶、超氧化物歧化酶和谷胱甘肽过氧化物酶活性降低33.5%-48.5%；核因子κB（NF-κB）激活增加2.3倍；核因子（红系衍生2）样2（Nrf2）信号传导受损38.9%。 结论：甘氨酸是一种功能性氨基酸，能够保护小鼠肝脏免受LPS诱导的损伤。
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