胎盘炎症和氧化应激水平可以预测儿童长期的糖代谢健康，来自队列研究的新证据

Associations of Placental Inflammation and Oxidative Stress Biomarkers with Glucolipid Metabolism in Children: A Birth Cohort Study in China

胎盘炎症和氧化应激生物标志物与儿童糖脂代谢的关系：一项来自中国的出生队列研究

 Author: Jixing Zhou, Yuzhu Teng, Jiajun Ouyang, Penggui Wu, Juan Tong, Guopeng Gao, Shuangqin Yan, Fangbiao Tao, Kun Huang

Source: Journal of the American Heart Association

DOI: 10.1161/JAHA.124.035754.

Abstract

Background: The maternal intrauterine immune environment may affect offspring long-term health. We aimed to investigate the association between the intrauterine placental immunological milieu and glycolipid metabolic health in children.

Methods and results: This study enrolled 1803 mother-child pairs from the Ma'anshan birth cohort (2013-2014). Placental mRNA expression of inflammatory cytokines (interleukin-1β [IL-1β], IL-10, monocyte chemoattractant protein-1, tumor necrosis factor-α, IL-4, IL-6, IL-8, C-reactive protein, and interferon-γ) and oxidative stress biomarkers (heme oxygenase-1, hypoxia-inducible factor-1alpha, and glucose-related protein 78) was quantified using real-time quantitative polymerase chain reaction. Fasting blood glucose, insulin, triglycerides, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and total cholesterol were assessed at 5 to 6 years old. Statistical analyses included multiple linear regression, binary logistic regression, restricted cubic spline model, and the Bayesian kernel machine regression model. Placental inflammatory cytokines (IL-1β, monocyte chemoattractant protein-1, C-reactive protein, IL-6, IL-8, IL-10) and oxidative stress biomarkers (heme oxygenase-1, hypoxia-inducible factor-1alpha, glucose-related protein 78) showed positive associations with children's fasting blood glucose levels. Heme oxygenase-1 and glucose-related protein 78 exhibited negative correlations with children's fasting insulin levels. Elevated IL-6, heme oxygenase-1, hypoxia-inducible factor-1alpha, and glucose-related protein 78 were associated with increased risk of prediabetes in children. Overall upregulation of placental proinflammatory cytokines and oxidative stress factors mRNA expression correlated with higher prediabetes risk in children. Bayesian kernel machine regression analysis indicated a joint positive effect of the 12 placental inflammation and oxidative stress mixtures on children’s risk of high fasting blood glucose.

Conclusions: This exploratory study underscores significant correlations between maternal intrauterine placental inflammation, oxidative stress markers, and offspring fasting blood glucose and insulin levels. These findings highlight the potential role of intrauterine holistic immunity in shaping offspring glucose metabolism health.

Keywords: children; cohort; glucose; inflammation; placenta.

摘要

背景：母体宫内免疫环境可能会影响后代的长期健康。我们旨在研究宫内胎盘免疫环境与儿童糖脂代谢健康之间的关系。

方法与结果：本研究纳入了马鞍山优生优育队列（2013~2014年）中的1803对母子对。采用实时定量聚合酶链反应对胎盘中炎症细胞因子（IL-1β、IL-10、MCP-1、TNF-α、IL-4、IL-6、IL-8、CRP、IFN-γ）和氧化应激生物标志物（HO-1、HIF-1α、GRP78）的 mRNA 表达进行定量。对 5 ~ 6 岁儿童的空腹血糖、胰岛素、甘油三酯、高密度脂蛋白胆固醇、低密度脂蛋白胆固醇和总胆固醇进行了评估。统计分析包括多元线性回归、二元逻辑回归、限制性三次样条模型和贝叶斯核机器回归模型。胎盘炎症细胞因子（IL-1β、MCP-1、CRP、IL-6、IL-8、IL-10）和氧化应激生物标志物（HO-1、HIF-1α、GRP78）与儿童的空腹血糖水平呈正相关。HO-1 和GRP 78 与儿童的空腹胰岛素水平呈负相关。IL-6、HO-1、HIF-1α和GRP78的升高与儿童罹患糖尿病前期的风险增加有关。胎盘促炎细胞因子和氧化应激因子 mRNA 表达的整体上调与儿童患糖尿病前期风险的增加有关。贝叶斯核机器回归分析表明，12种胎盘炎症和氧化应激混合物对儿童空腹血糖过高的风险具有共同的正效应。

结论：这项探索性研究强调了母体宫内胎盘炎症、氧化应激标记物与后代空腹血糖和胰岛素水平之间的显著相关性。这些发现强调了宫内整体免疫在塑造后代糖代谢健康中的潜在作用。

关键词：儿童；队列；葡萄糖；炎症；胎盘。