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黄芪甲苷IV通过维生素D3上调蛋白1/核因子κB信号通路减轻氧化应激和抑制炎症来改善坏死性小肠结肠炎。

Astragaloside IV ameliorates necrotizing enterocolitis by attenuating oxidative stress and suppressing inflammation via the vitamin D3-upregulated protein 1/NF-κB signaling pathway.

作者信息

Cai Zhiyong, Liu Jindi, Bian Hongliang, Cai Jinlan

机构信息

Newborn Department, Yancheng Maternity and Child Health Care Hospital, Yancheng, Jiangsu 224000, P.R. China.

出版信息

Exp Ther Med. 2016 Oct;12(4):2702-2708. doi: 10.3892/etm.2016.3629. Epub 2016 Aug 30.

Abstract

Astragaloside IV (AS-IV) is a flavonoid from the plant (Fisch) Bge that has a wide range of therapeutic effects. The aim of the present study was to examine the effect of AS-IV on rats with necrotizing enterocolitis (NEC) under oxidative stress and inflammation. Newborn Sprague-Dawley rats were induced with NEC by asphyxia and hypothermia applied on 3 consecutive days. The rats were orally administered AS-IV at 25, 50 and 75 mg/kg for 4 days. The results revealed that AS-IV administration prevented NEC-induced decrease in the concentration of malondialdehyde and myeloperoxidase, and increase in the activity of glutathione (GSH) and superoxide dismutase in murine models. AS-IV also inhibited NEC-induced elevation in the levels of interleukin (IL)-6, IL-1β, tumor necrosis factor-α and nuclear factor (NF)-κB. The effects of AS-IV were achieved under inflammation and oxidative stress. Western blotting demonstrated that AS-IV substantially inhibited the phosphorylated (p)-IκBα, NF-κBp65, p-NF-κBp65 protein levels and increased vitamin D3 upregulated protein 1 (VDUP1) and IκBα protein levels. These data indicate that AS-IV may be effective in the protection of NEC-induced ileum degeneration by inhibiting the levels of inflammatory markers and oxidative stress via the regulation of the VDUP1/NF-κB signaling pathway.

摘要

黄芪甲苷IV(AS-IV)是一种从植物蒙古黄芪(Fisch)Bge中提取的黄酮类化合物,具有广泛的治疗作用。本研究的目的是研究AS-IV在氧化应激和炎症条件下对坏死性小肠结肠炎(NEC)大鼠的影响。通过连续3天施加窒息和低温诱导新生Sprague-Dawley大鼠发生NEC。将大鼠分别以25、50和75 mg/kg的剂量口服给予AS-IV,持续4天。结果显示,在小鼠模型中,给予AS-IV可防止NEC诱导的丙二醛和髓过氧化物酶浓度降低,以及谷胱甘肽(GSH)和超氧化物歧化酶活性增加。AS-IV还抑制了NEC诱导的白细胞介素(IL)-6、IL-1β、肿瘤坏死因子-α和核因子(NF)-κB水平升高。AS-IV的这些作用是在炎症和氧化应激条件下实现的。蛋白质印迹法表明,AS-IV可显著抑制磷酸化(p)-IκBα、NF-κBp65、p-NF-κBp65蛋白水平,并增加维生素D3上调蛋白1(VDUP1)和IκBα蛋白水平。这些数据表明,AS-IV可能通过调节VDUP1/NF-κB信号通路抑制炎症标志物水平和氧化应激,从而有效保护NEC诱导的回肠变性。

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