Abstract

This study investigated changes in oxidative stress and the relevant mechanisms in the liver of goats fed a high-concentrate (HC) diet for 5 weeks. Twelve goats were randomly assigned to a low-concentrate (concentrate-to-forage = 55:45, LC, n = 6) or HC diet (concentrate-to-forage = 90:10, n = 6), with dry matter as the base. Enzyme activity assays, real-time polymerase chain reaction and western blotting were used to evaluate antioxidant parameters and gene expression in the liver. Superoxide dismutase (SOD), glutathione peroxidase (GPx), catalase (CAT), total nitric oxide synthase activity and total antioxidant capacity (T-AOC) in the liver declined (p < .01) in HC-fed goats compared to those in LC-fed goats. The mRNA levels of GPX1, CAT and SOD1 were down-regulated (3.69, 47.37 and 27.61%, respectively) in HC-fed goats compared to those in LC-fed goats. Furthermore, glutathione S-transferase M1 (GSTM1) was upregulated (466.35%, p < .01) in the liver of HC-fed goats. The mRNA and protein levels of the nuclear factor E2-related factor 2 (NRF2) and total glucocorticoid receptor (GR) declined (p < .05) in HC-fed goats (by 28.57, 33.1, 30.85 and 34%, respectively). However, the nuclear translocation of GR increased (p < .05; by 44.75%) in HC-fed goats. Negative correlations were detected for hepatic nuclear GR protein expression with hepatic CAT activity and GPx activity. In conclusion, feeding an HC diet to goats for 5 weeks suppressed NRF2-dependent antioxidant responses and enhanced GR nuclear translocation in the liver.

• Highlights

• Feeding goats high-concentrate diets suppresses NRF2-dependent antioxidant responses in liver, downregulating NRF2 and altering SOD1, GPx and CAT activity.

• This suppression of NRF2-dependent antioxidant responses is associated with GR activation in the liver of goats.

摘要

这项研究调查了饲喂高浓度（HC）饲料5周的山羊肝脏中氧化应激的变化及其相关机制。将十二只山羊随机分配至低浓度饲料（精饲料为55：45，LC，n  = 6）或HC饲料（饲料精料为90：10，n  = 6），干物质为基地。酶活性测定，实时聚合酶链反应和蛋白质印迹法用于评估肝脏中的抗氧化剂参数和基因表达。 与HC饲喂的山羊相比，肝脏中的超氧化物歧化酶（SOD），谷胱甘肽过氧化物酶（GPx），过氧化氢酶（CAT），肝脏总一氧化氮合酶活性和总抗氧化能力（T-AOC）降低（p <.01）。 LC饲养的山羊。GPX1的mRNA水平，CAT和SOD1表达下调（3.69，47.37和27.61％，分别地）在HC-馈送山羊相比，那些在LC-馈送山羊。此外，在以HC喂养的山羊的肝脏中，谷胱甘肽S-转移酶M1（GSTM1）被上调（466.35％，p <.01）。HC喂养山羊的核因子E2相关因子2（NRF2）和总糖皮质激素受体（GR）的mRNA和蛋白质水平下降（p <.05）（分别下降28.57、33.1、30.85和34％）。然而，遗传资源的核易位增加（p <.05; HC饲喂的山羊中的比例提高了44.75％）。检测到肝核GR蛋白表达与肝CAT活性和GPx活性呈负相关。总之，给山羊喂食HC饮食5周可抑制NRF2依赖的抗氧化反应并增强肝脏中GR核的转运。

• 强调

• 喂山羊高浓度饮食可以抑制肝脏中NRF2依赖性的抗氧化反应，下调NRF2并改变SOD1，GPx和CAT活性。

• NRF2依赖性抗氧化剂反应的这种抑制与山羊肝中GR的活化有关。