妊娠期糖尿病会通过胎盘炎症和自噬增加新生儿感染风险。
Gestational diabetes mellitus in women increased the risk of neonatal infection via inflammation and autophagy in the placenta.
作者信息
Li Yi-Xiao, Long Deng-Lu, Liu Jia, Qiu Di, Wang Jingyun, Cheng Xin, Yang Xuesong, Li Rui-Man, Wang Guang
机构信息
The First Affiliate Hospital of Jinan University.
International Joint Laboratory for Embryonic Development & Prenatal Medicine, Division of Histology and Embryology, Medical College.
出版信息
Medicine (Baltimore). 2020 Oct 2;99(40):e22152. doi: 10.1097/MD.0000000000022152.
BACKGROUND
Gestational diabetes mellitus (GDM) produces numerous problems for maternal and fetal outcomes. However, the precise molecular mechanisms of GDM are not clear.
METHODS
In our study, we randomly assigned 22 pregnant women with fasting glucose concentrations, 1 hour oral glucose tolerance test (1H-OGTT) and 2 hour oral glucose tolerance test (2H-OGTT), different than 28 normal pregnant women from a sample of 107 pregnant women at the First Affiliated Hospital of Jinan University in China. Lipopolysaccharide (LPS), interleukin 1 alpha (IL-1α), interleukin-6 (IL-6), interleukin-8 (IL-8) and tumor necrosis factor alpha (TNF-α) were measured from blood plasma of pregnant women and umbilical arteries using ultraviolet spectrophotometry. Hematoxylin & Eosin (H&E), Periodic acid-Schiff (PAS) or Masson staining were performed to examine whether diabetes mellitus altered the morphology of placenta. Quantitative PCR (Q-PCR), western blotting and immunofluorescent staining were performed to examine whether diabetes mellitus and autophagy altered the gene expressions of the placental tissue.
RESULTS
We found that women with GDM exhibited increased placental weight and risk of neonatal infection. The concentrations of IL-6 protein and IL-8 protein in GDM were increased in both maternal and umbilical arterial blood. H&E, Masson and PAS staining results showed an increased number of placental villi and glycogen deposition in patients with GDM, but no placental sclerosis was found. Q-PCR results suggested that the expression levels of HIF-1α and the toll like receptor 4 (TLR4)/ myeloid differential protein-88 (MyD88)/ nuclear factor kappa-B (NF-κB) pathway were increased in the GDM placenta. Through Western Blotting, we found that the expression of NF-kappa-B inhibitor alpha (IKBα) and Nuclear factor-κB p65 (NF-κB p65) in GDM placenta was significantly enhanced. We also showed that the key autophagy-related genes, autophagy-related 7 (ATG7) and microtubule-associated protein 1A/1B-light chain 3 (LC3), were increased in GDM compared with normal pregnant women.
CONCLUSIONS
Our results suggest that women with GDM exhibit an increased risk of neonatal infection via inflammation and autophagy in the placenta.
背景
妊娠期糖尿病（GDM）会给母婴结局带来诸多问题。然而，GDM的确切分子机制尚不清楚。
方法
在我们的研究中，从中国暨南大学附属第一医院的107名孕妇样本中，随机选取22名空腹血糖浓度、口服葡萄糖耐量试验1小时（1H - OGTT）和口服葡萄糖耐量试验2小时（2H - OGTT）结果与28名正常孕妇不同的孕妇。采用紫外分光光度法测定孕妇血浆和脐动脉血中脂多糖（LPS）、白细胞介素1α（IL - 1α）、白细胞介素 - 6（IL - 6）、白细胞介素 - 8（IL - 8）和肿瘤坏死因子α（TNF - α）的含量。进行苏木精 - 伊红（H&E）、过碘酸 - 希夫（PAS）或Masson染色，以检查糖尿病是否改变胎盘形态。进行定量聚合酶链反应（Q - PCR）、蛋白质免疫印迹法和免疫荧光染色，以检查糖尿病和自噬是否改变胎盘组织的基因表达。
结果
我们发现，患有GDM的女性胎盘重量增加，新生儿感染风险增加。GDM患者母血和脐动脉血中IL - 6蛋白和IL - 8蛋白浓度均升高。H&E、Masson和PAS染色结果显示，GDM患者胎盘绒毛数量增加，糖原沉积增加，但未发现胎盘硬化。Q - PCR结果表明，GDM胎盘组织中缺氧诱导因子1α（HIF - 1α）以及Toll样受体4（TLR4）/髓样分化蛋白88（MyD88）/核因子κB（NF - κB）信号通路的表达水平升高。通过蛋白质免疫印迹法，我们发现GDM胎盘组织中NF - κB抑制蛋白α（IKBα）和核因子 - κB p65（NF - κB p65）的表达显著增强。我们还发现，与正常孕妇相比，GDM患者中自噬相关关键基因自噬相关蛋白7（ATG7）和微管相关蛋白1A/1B轻链3（LC3）的表达增加。
结论
我们的结果表明，患有GDM的女性胎盘通过炎症和自噬增加了新生儿感染的风险。
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