College of Animal Science and Technology, Nanjing Agricultural University, Nanjing 210095, China.
Biomed Res Int. 2020 Jul 18;2020:7402645. doi: 10.1155/2020/7402645. eCollection 2020.
Abnormal lipid metabolism, oxidative stress (OS), and inflammation play a pivotal role in the increased susceptibility to neonatal fatty liver diseases associated with intrauterine growth retardation (IUGR). This study was firstly conducted to investigate whether resveratrol could alleviate IUGR-induced hepatic lipid accumulation, alteration of redox and immune status in a sucking piglet model and explore the possible mechanisms at transcriptional levels. A total of 36 pairs of 7 d old male normal birth weight (NBW) and IUGR piglets were orally fed with either 80 mg resveratrol/kg body weight/d or 0.5% carboxymethylcellulose sodium for a period of 14 days, respectively. Compared with the NBW piglets, the IUGR piglets displayed compromised growth performance and liver weight, reduced plasma free fatty acid (FFA) level, increased hepatic OS, abnormal hepatic lipid accumulation and weakened hepatic immune function, and hepatic aberrant transcriptional expression of some genes such as heme oxygenase 1, superoxide dismutase 1, sterol regulatory element-binding protein 1c, stearoyl-CoA desaturase 1, liver fatty acid-binding proteins 1, toll-like receptor 4, and tumor necrosis factor alpha (TNF-). Oral administration of resveratrol to piglets decreased the levels of FFA and total triglycerides (TG) in the plasma and hepatic TNF- concentration, and increased glutathione reductase activity and reduced glutathione level in the liver. Resveratrol restored the increased alanine aminotransferase activity in the plasma of IUGR piglets. Treatment with resveratrol ameliorated the increased hepatic malondialdehyde, protein carbonyl, TG, and FFA concentrations induced by IUGR. Resveratrol treatment alleviated the reduced lipoprotein lipase activity and its mRNA expression as well as TNF- gene expression in the liver of IUGR piglets. Hepatic glutathione peroxidase 1 and monocyte chemotactic protein 1 genes expression of piglets was upregulated by oral resveratrol administration. In conclusion, resveratrol administration plays a beneficial role in hepatic redox status and lipid balance of the IUGR piglets.
异常的脂质代谢、氧化应激(OS)和炎症在与宫内生长迟缓(IUGR)相关的新生儿脂肪肝疾病的易感性增加中起着关键作用。本研究首先旨在探讨白藜芦醇是否可以减轻 IUGR 诱导的仔猪模型肝内脂质积累、氧化还原和免疫状态的改变,并在转录水平上探讨可能的机制。总共 36 对 7 日龄正常出生体重(NBW)和 IUGR 仔猪分别口服 80mg/kg 体重/天的白藜芦醇或 0.5%羧甲基纤维素钠 14 天。与 NBW 仔猪相比,IUGR 仔猪表现出生长性能和肝重受损、血浆游离脂肪酸(FFA)水平降低、肝 OS 增加、肝内脂质积累异常、肝免疫功能减弱,以及一些基因如血红素加氧酶 1、超氧化物歧化酶 1、固醇调节元件结合蛋白 1c、硬脂酰辅酶 A 去饱和酶 1、肝脂肪酸结合蛋白 1、Toll 样受体 4 和肿瘤坏死因子-α(TNF-α)的肝转录表达异常。白藜芦醇口服给药降低了仔猪血浆和肝 TNF-α浓度中的 FFA 和总三酰甘油(TG)水平,增加了肝谷胱甘肽还原酶活性和降低了肝还原型谷胱甘肽水平。白藜芦醇恢复了 IUGR 仔猪血浆中升高的丙氨酸氨基转移酶活性。白藜芦醇治疗改善了 IUGR 引起的肝丙二醛、蛋白质羰基、TG 和 FFA 浓度增加。白藜芦醇治疗减轻了 IUGR 仔猪肝内脂蛋白脂酶活性及其 mRNA 表达以及 TNF-α基因表达的降低。口服白藜芦醇给药后,仔猪肝谷胱甘肽过氧化物酶 1 和单核细胞趋化蛋白 1 基因表达上调。总之,白藜芦醇给药在 IUGR 仔猪的肝氧化还原状态和脂质平衡中发挥有益作用。