目的: 探讨妊娠糖尿病（gestational diabetes mellitus,GDM）患者外周血单核细胞（PBMCs）中内质网应激标志物在胎盘功能障碍中的作用。方法: 选取2022年1月―2023年6月在我院门诊就诊或住院治疗的100名30~32周妊娠的单胎患者。其中,50名门诊就诊患者是妊娠期血糖调节正常的对照组。50名住院治疗患者在妊娠中期（妊娠24~28周）出现GDM选做研究组,通过饮食或胰岛素治疗实现血糖控制。PCR分析内质网应激（endoplasmic reticulum stress,ERs）途径相关标志物表达,包括激活转录因子4（ATF4）和增强子结合蛋白同源蛋白（CHOP）。结果: 与对照组相比,GDM组空腹血糖、75 g葡萄糖负荷后2 h血糖、可溶性FMS样酪氨酸激酶1/胎盘生长因子（sFlt-1/PLGF）比值和sFlt-1显著增加,和PLGF水平显著降低。与对照组相比,GDM组单核细胞中ATF4和CHOP基因表达显著增加。对于整个队列,外周血单核细胞中ATF4和CHOP基因表达随着sFlt-1/PLGF比值的增加而逐渐增加（F=60.79、25.58,均P<0.001）。相关性分析显示ATF4和CHOP基因表达与sFlt-1/PLGF比值呈显著正相关。受试者工作特征曲线（ROC）分析发现,ATF4预测GDM的AUC为0.801,敏感度为92.1%,特异度为76.0%;CHOP预测GDM的AUC为0.738,其敏感度为75%,特异度为80%。结论: GDM对胎盘功能有不良影响。ATF4和CHOP可能是早期检测胎儿胎盘内皮功能障碍的潜在标志物。
Abstract
Objective To investigate the role of endoplasmic reticulum stress markers in peripheral blood mononuclear cells (PBMCs) of patients with gestational diabetes mellitus (GDM) in placental dysfunction. Methods Select 100 singleton patients with 30-32 weeks of pregnancy who received outpatient or inpatient treatment at our hospital from January 2022 to June 2023. Among them, 50 outpatient patients were the control group with normal blood glucose regulation during pregnancy.50 hospitalized patients with GDM during mid pregnancy (24-28 weeks of pregnancy) were selected as the study group to achieve blood glucose control through diet or insulin therapy. Expression of endoplasmic reticulum stress (ERs) pathway related biomarkers, including activating transcription factor 4(ATF4) and enhancer binding protein homologous protein (CHOP), analyzed by PCR Results Compared with the control group, fasting blood glucose, blood glucose at 2 hours after 75 g glucose loading, sFlt-1 and sFlt-1/PLGF ratio in GDM group increased significantly, and PLGF level decreased significantly. Compared with the control group, the expression of ATF4 and CHOP genes in monocytes in GDM group increased significantly. For the whole cohort, the expression of ATF4 and CHOP genes in peripheral blood monocytes increased with the increase of sFlt-1/PLGF ratio (F=60.79, 25.58, all P<0.001). Correlation analysis showed that the expression of ATF4 and CHOP genes was positively correlated with the ratio of sFlt-1/PLGF. According to ROC analysis, it was found that the AUC of ATF4 in predicting GDM was 0.801, the sensitivity was 92.1%, and the specificity was 76.0%. The AUC of CHOP for predicting GDM was 0.738, and it had a sensitivity of 75% and a specificity of 80%. Conclusions GDM has adverse effects on placental function. ATF4 and CHOP may be potential markers for early detection of placental endothelial dysfunction in the fetus.
关键词
妊娠糖尿病 /
外周血单核细胞 /
内质网应激 /
胎盘功能障碍
Key words
gestational diabetes mellitus /
peripheral blood mononuclear cells /
endoplasmic reticulum stress /
placental dysfunction
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基金
山东省医药卫生科技项目“妊娠期糖尿病患者中内质网应激标志物在胎盘功能障碍中的作用研究”（202104090192）
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