Department of Obstetrics, Guizhou Provincial People's Hospital, Guiyang, People's Republic of China.
J Cell Biochem. 2019 Sep;120(9):15310-15319. doi: 10.1002/jcb.28798. Epub 2019 May 3.
Gestational diabetes mellitus (GDM) is a common disorder characterized by abnormal glucose metabolism during pregnancy, affecting 2% to 5% of pregnant women. Currently, clinical treatment for GDM is very limited. The present study was designed to investigate the effect and underlying molecular mechanism of tertiary butylhydroquinone (TBHQ) in a pregnant C57BL/KsJ-Lep db/+ (referred to as db+) GDM mouse model. The results showed that nonpregnant db/+ mice did not show a diabetic phenotype, and TBHQ had no effect on glucose and insulin tolerance in these mice. Moreover, in db/+ pregnant mice exhibiting typical diabetes symptoms, such as hyperglycemia and hypoinsulinemia, TBHQ could remarkably decrease the blood glucose level, increase insulin level, and improve glucose and insulin intolerance. The results also revealed that TBHQ could inhibit oxidative stress in pregnant db/+ mice. Furthermore, TBHQ greatly improved offspring survival rate, glucose metabolism, and insulin tolerance. In addition, TBHQ inhibited oxidative stress by reducing malondialdehyde (MDA) and reactive oxygen species (ROS) levels and increased superoxide dismutase (SOD), and glutathione peroxidase (GPx) activities. Moreover, we found that TBHQ activated the nuclear factor erythroid 2-related factor 2 (Nrf2), thereby increasing the levels of Nrf2, and ultimately upregulating the expression of heme oxygenase 1 (NO-1) and superoxide dismutase 2 (SOD2). In conclusion, our findings demonstrated that TBHQ alleviated GDM via Nrf2 activation.
妊娠期糖尿病（GDM）是一种常见的疾病，其特征是妊娠期间葡萄糖代谢异常，影响 2%至 5%的孕妇。目前，GDM 的临床治疗方法非常有限。本研究旨在探讨叔丁基对苯二酚（TBHQ）在 C57BL/KsJ-Lep db/+（简称 db+）妊娠 GDM 小鼠模型中的作用及其潜在的分子机制。结果表明，未妊娠的 db+/+ 小鼠没有表现出糖尿病表型，TBHQ 对这些小鼠的葡萄糖和胰岛素耐量没有影响。此外，在表现出典型糖尿病症状（如高血糖和胰岛素血症）的 db+/+ 妊娠小鼠中，TBHQ 可显著降低血糖水平，增加胰岛素水平，并改善葡萄糖和胰岛素耐量。结果还表明，TBHQ 可抑制妊娠 db+/+ 小鼠的氧化应激。此外，TBHQ 大大提高了后代的存活率、葡萄糖代谢和胰岛素耐量。此外，TBHQ 通过降低丙二醛（MDA）和活性氧（ROS）水平以及增加超氧化物歧化酶（SOD）和谷胱甘肽过氧化物酶（GPx）的活性来抑制氧化应激。此外，我们发现 TBHQ 激活了核因子红细胞 2 相关因子 2（Nrf2），从而增加了 Nrf2 的水平，并最终上调了血红素加氧酶 1（NO-1）和超氧化物歧化酶 2（SOD2）的表达。总之，我们的研究结果表明，TBHQ 通过激活 Nrf2 缓解了 GDM。
