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维生素E补充剂通过核因子-红细胞2相关因子2/血红素加氧酶-1信号通路预防小鼠妊娠期糖尿病。

Vitamin E Supplement Protects Against Gestational Diabetes Mellitus in Mice Through nuclear factor-erythroid factor 2-related factor 2/heme oxygenase-1 Signaling Pathway.

作者信息

Lin Bozhu, Zhang Xiaorong

机构信息

Gynaecology and Obstetrics Department, Longyan People's Hospital, Longyan, People's Republic of China.

Neonatal Department, Longyan People's Hospital, Longyan, People's Republic of China.

出版信息

Diabetes Metab Syndr Obes. 2023 Mar 1;16:565-574. doi: 10.2147/DMSO.S397255. eCollection 2023.

Abstract

BACKGROUND

Gestational diabetes mellitus (GDM) is the most common pregnant disorder worldwide. In this study, we aimed to explore whether vitamin E (VE) treatment alone could protect against GDM in a mouse model.

METHODS

6-week-old C57BL/6J female mice were fed on high-fat diet for two weeks and continued with high-fat diet after pregnancy to induce GDM. The pregnant mice were orally administrated with 2.5, 25 or 250 mg/kg VE twice per day during pregnancy together with high-fat diet. Oral glucose tolerance test, insulin amounts, oxidative stress and inflammation were then measured.

RESULTS

Only 250 mg/kg VE could improve glucose tolerance and insulin level in pregnant mice. VE (250 mg/kg) effectively inhibited GDM-induced hyperlipidemia, and secretion of inflammatory cytokines such as tumor necrosis factor-α and interleukin-6. VE also significantly ameliorated maternal oxidative stress at the late stage of pregnancy, and also improved reproductive outcomes, including increasing the litter size and birth weight in GDM mice. Moreover, VE also activated GDM-reduced nuclear factor-erythroid factor 2-related factor 2 (Nrf2) / heme oxygenase-1 signaling pathway in the maternal liver tissues of GDM mice.

CONCLUSION

Our data clearly demonstrated that 250 mg/kg VE twice a day during pregnancy could significantly ameliorate the symptoms of GDM by alleviating oxidative stress, inflammation, hyperglycemia, and hyperlipidemia through Nrf2/HO-1 signaling pathway in GDM mice. Thus, additional VE supplement might be beneficial to GDM.

摘要

背景

妊娠期糖尿病(GDM)是全球最常见的妊娠疾病。在本研究中,我们旨在探讨单独使用维生素E(VE)治疗是否能在小鼠模型中预防GDM。

方法

6周龄的C57BL/6J雌性小鼠喂食高脂饮食两周,怀孕后继续高脂饮食以诱导GDM。怀孕小鼠在孕期与高脂饮食一起每天口服2.5、25或250mg/kg VE两次。然后测量口服葡萄糖耐量试验、胰岛素量、氧化应激和炎症。

结果

只有250mg/kg VE能改善怀孕小鼠的葡萄糖耐量和胰岛素水平。VE(250mg/kg)有效抑制GDM诱导的高脂血症以及肿瘤坏死因子-α和白细胞介素-6等炎性细胞因子的分泌。VE还显著改善了孕期晚期母体的氧化应激,并且改善了生殖结局,包括增加GDM小鼠的窝产仔数和出生体重。此外,VE还激活了GDM小鼠母体肝脏组织中GDM降低的核因子-红细胞2相关因子2(Nrf2)/血红素加氧酶-1信号通路。

结论

我们的数据清楚地表明,孕期每天两次给予250mg/kg VE可通过Nrf2/HO-1信号通路减轻氧化应激、炎症、高血糖和高脂血症,从而显著改善GDM小鼠的症状。因此,额外补充VE可能对GDM有益。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4745/9985888/8b727da47a35/DMSO-16-565-g0001.jpg

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