凤凰素-20 可改善实验性小鼠模型的妊娠糖尿病（GDM）症状和胎盘损伤。
Phoenixin-20 ameliorates gestational diabetes mellitus (GDM) symptoms and placental insults in an experimental mouse model.
机构信息
Department of gynaecology and obstetrics, Longyan First Hospital, Affiliated to Fujian Medical University, Longyan, Fujian province, 364000, China.
Department of gynaecology and obstetrics, Longyan First Hospital, Affiliated to Fujian Medical University, Longyan, Fujian province, 364000, China.
出版信息
Int Immunopharmacol. 2021 Dec;101(Pt A):108171. doi: 10.1016/j.intimp.2021.108171. Epub 2021 Oct 1.
BACKGROUND AND PURPOSE
Gestational diabetes mellitus (GDM) is a complication commonly observed in pregnancy, closely associated with increased oxidative stress, inflammatory response, and endoplasmic reticulum (ER) stress. Phoenixin-20 (PNX-20) is a newly reproductive hormone from the hypothalamus that has displayed pleiotropic effects. The promising inhibitory effects of PNX-20 on inflammation have recently been widely reported. The present study aims to investigate the protective effect of PNX-20 on GDM induced placental insults.
METHODS
A GDM model was established on C57BLKsJ mice. The expression level of GPR173 was evaluated using RT-PCR and western blotting analysis. The serum level of glucose, insulin, lipid profiles, and oxidative stress indicators were detected with commercial kits. Fetal analysis was performed to evaluate the reproductive ability. ELISA was used to detect the production of inflammatory factors. The expressions of p-eIF-2α, ATF4, and GRP78 were evaluated with western blotting assay.
RESULTS
Firstly, we found that GPR173 is expressed in the placenta tissue. Secondly, the elevated blood glucose level and lipid level, declined serum insulin level, fetus alive ratio, fetal and placenta weight, and shorten crown-rump length, were observed in the placenta tissue of GDM mice, which were reversed by treatment with PNX-20. Thirdly, the excessively released inflammatory factors and activated oxidative stress in GDM mice were alleviated by the administration of PNX-20. Lastly, the activated eIF-2α/ATF4 ER stress signaling pathway in GDM mice was dramatically suppressed by PNX-20.
CONCLUSION
Our data revealed a protective property of PNX-20 against placental insults resulted from GDM.
背景与目的
妊娠糖尿病（GDM）是一种常见的妊娠并发症，与氧化应激、炎症反应和内质网（ER）应激密切相关。凤凰素-20（PNX-20）是一种来自下丘脑的新的生殖激素，具有多种作用。最近有研究广泛报道，PNX-20 对炎症具有有希望的抑制作用。本研究旨在探讨 PNX-20 对 GDM 诱导的胎盘损伤的保护作用。
方法
在 C57BLKsJ 小鼠上建立 GDM 模型。采用 RT-PCR 和 Western blot 分析评估 GPR173 的表达水平。采用商业试剂盒检测血清中葡萄糖、胰岛素、血脂谱和氧化应激指标。进行胎儿分析以评估生殖能力。采用 ELISA 检测炎症因子的产生。采用 Western blot 检测 p-eIF-2α、ATF4 和 GRP78 的表达。
结果
首先，我们发现 GPR173 在胎盘组织中表达。其次，在 GDM 小鼠的胎盘组织中观察到血糖和血脂水平升高、血清胰岛素水平下降、活胎比例、胎儿和胎盘重量以及胎头臀长缩短，而 PNX-20 处理可逆转这些变化。第三，PNX-20 可减轻 GDM 小鼠过度释放的炎症因子和激活的氧化应激。最后，PNX-20 可显著抑制 GDM 小鼠中激活的 eIF-2α/ATF4 ER 应激信号通路。
结论
我们的数据揭示了 PNX-20 对 GDM 引起的胎盘损伤的保护作用。
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