Zearalenone (ZEA) contamination of feed affects animal husbandry and the human health. Currently, the molecular mechanism underlying small intestine-related diseases caused by ZEA-induced oxidative stress is not well understood. In this study, we aimed to identify the mechanisms involved in ZEA (0.5-1.5 mg/kg)-induced oxidative stress in the ileum and mesenteric lymph nodes (MLNs) and the role of the Kelch-like erythroid cell-derived protein with CNC homology-associated protein 1 (Keap1)-nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway in post-weaning gilts. Forty post-weaning gilts (Landrace × Yorkshire × Duroc) with an average body weight of 14.01 ± 0.86 kg were randomly allocated to four groups and fed a corn-soybean meal basal diet supplemented with < 0.1, 0.5, 1.0, or 1.5 mg/kg ZEA. The results showed that the activity of total superoxide dismutase and glutathione peroxidase decreased (p < 0.05) linearly and quadratically and that the content of malondialdehyde increased (p < 0.05) quadratically in the ileum and MLNs with increasing ZEA in the diet. Immunohistochemical analysis showed that the expression of Nrf2 and glutathione peroxidase 1 (Gpx1) immunoreactive proteins in the ileum and MLNs were significantly enhanced with increasing ZEA. The relative mRNA and protein expression of Nrf2, Gpx1, quinone oxidoreductase 1 (Nqo1), hemeoxygenase 1 (Ho1), modifier subunit of glutamate-cysteine ligase (Gclm), and catalytic subunit of glutamate-cysteine ligase (Gclc) increased (p < 0.05) linearly and quadratically, and the relative mRNA and protein expression of Keap1 decreased (p < 0.05) linearly and quadratically in the ileum with increasing ZEA concentrations in the diet. Further, the relative mRNA and protein expression of Nrf2 and Gpx1 increased (p < 0.05) linearly and quadratically, and the relative mRNA and protein expression of Nqo1, Ho1, and Gclm decreased (p < 0.05) quadratically in the MLNs as ZEA concentrations increased in the diet. Our results provide valuable genetic information on ZEA-induced oxidative stress in the ileum and MLNs of post-weaning gilts and have elucidated the key regulatory genes involved in the Keap1-Nrf2 signaling pathway. Results indicated that the Keap1-Nrf2 signaling pathway might be a key target to further prevent and treat ZEA-induced injury to the ileum in post-weaning gilts.

中文翻译：

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断奶后仔猪回肠和肠系膜淋巴结中玉米赤霉烯酮诱导的氧化应激和Keap1-Nrf2信号通路相关基因表达的影响。

饲料中玉米赤霉烯酮（ZEA）的污染会影响畜牧业和人类健康。目前，由ZEA诱导的氧化应激引起的小肠相关疾病的分子机制尚不十分清楚。在这项研究中，我们旨在确定ZEA（0.5-1.5 mg / kg）诱导的回肠和肠系膜淋巴结（MLNs）氧化应激的机制，以及Kelch样类红细胞衍生蛋白在CNC中的作用断奶后后备母猪的同源相关蛋白1（Keap1）-核因子红系2相关因子2（Nrf2）信号通路。将四十只平均体重为14.01±0.86 kg的断奶后备母猪（Landrace×Yorkshire×Duroc）随机分为四组，并饲喂补充了<0.1、0.5、1.0或1.5 mg /公斤ZEA。结果表明，随着日粮中ZEA的增加，回肠和MLN中总超氧化物歧化酶和谷胱甘肽过氧化物酶的活性呈线性和二次下降（p <0.05），丙二醛含量呈二次上升（p <0.05）。免疫组织化学分析显示，随着ZEA的增加，回肠和MLN中Nrf2和谷胱甘肽过氧化物酶1（Gpx1）免疫反应蛋白的表达显着增强。Nrf2，Gpx1，醌氧化还原酶1（Nqo1），血红素加氧酶1（Ho1），谷氨酸半胱氨酸连接酶（Gclm）的修饰子亚基和谷氨酸半胱氨酸连接酶（Gclc）的催化亚基的相对mRNA和蛋白质表达增加（p < 0.05）线性和二次方化，Keap1的相对mRNA和蛋白质表达降低（p <0。05）在回肠中线性和二次地随着饮食中ZEA浓度的增加而增加。此外，随着ZEA浓度的增加，MLN中Nrf2和Gpx1的相对mRNA和蛋白质表达呈线性和二次增加（p <0.05），Nqo1，Ho1和Gclm的相对mRNA和蛋白质表达也呈二次下降（p <0.05）。在饮食中。我们的结果为断奶后小母猪回肠和MLNs中ZEA诱导的氧化应激提供了有价值的遗传信息，并阐明了参与Keap1-Nrf2信号通路的关键调控基因。结果表明，Keap1-Nrf2信号通路可能是进一步预防和治疗断奶后小母猪ZEA引起的回肠损伤的关键靶标。Nrf2和Gpx1的相对mRNA和蛋白质表达呈线性和二次增长（p <0.05），Nqo1，Ho1和Gclm的相对mRNA和蛋白质表达随ZEA浓度的增加呈二次下降（p <0.05）。饮食。我们的结果为断奶后小母猪回肠和MLNs中ZEA诱导的氧化应激提供了有价值的遗传信息，并阐明了参与Keap1-Nrf2信号通路的关键调控基因。结果表明，Keap1-Nrf2信号通路可能是进一步预防和治疗断奶后小母猪ZEA引起的回肠损伤的关键靶标。Nrf2和Gpx1的相对mRNA和蛋白质表达呈线性和二次增长（p <0.05），Nqo1，Ho1和Gclm的相对mRNA和蛋白质表达随ZEA浓度的增加呈二次下降（p <0.05）。饮食。我们的结果为断奶后小母猪回肠和MLNs中ZEA诱导的氧化应激提供了有价值的遗传信息，并阐明了参与Keap1-Nrf2信号通路的关键调控基因。结果表明，Keap1-Nrf2信号通路可能是进一步预防和治疗断奶后小母猪ZEA引起的回肠损伤的关键靶标。05）随着饮食中ZEA浓度的增加，MLN呈二次方变化。我们的结果为断奶后小母猪回肠和MLNs中ZEA诱导的氧化应激提供了有价值的遗传信息，并阐明了参与Keap1-Nrf2信号通路的关键调控基因。结果表明，Keap1-Nrf2信号通路可能是进一步预防和治疗断奶后小母猪ZEA引起的回肠损伤的关键靶标。05）随着饮食中ZEA浓度的增加，MLN呈二次方变化。我们的结果为断奶后小母猪回肠和MLNs中ZEA诱导的氧化应激提供了有价值的遗传信息，并阐明了参与Keap1-Nrf2信号通路的关键调控基因。结果表明，Keap1-Nrf2信号通路可能是进一步预防和治疗断奶后小母猪ZEA引起的回肠损伤的关键靶标。